FDA expands Xarelto use to DVT, PE

The FDA today voted to expand the approved use of rivaroxaban (Xarelto, Janssen Pharmaceuticals) to include the treatment of deep vein thrombosis or pulmonary embolism.

The drug also now is approved to reduce the risk of recurrence of those two conditions after initial therapy, according to an FDA press release.

“Xarelto is the first oral anti-clotting drug approved to treat and reduce the recurrence of blood clots since the approval of warfarin nearly 60 years ago,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the release.
The FDA approved the expanded use under its priority review program, which allows for an expedited 6-month review for drugs that offer major advances in treatment or offer a treatment where none exist.
The approval comes after encouraging results from the three EINSTEIN studies, which involved more than 9,000 patients with thromboembolic events.
In July 2011, the FDA approved rivaroxaban to reduce the risk of DVT and PE after knee or hip replacement surgery. In November 2011, the agency approved the drug to reduce stroke risk individuals with non-valvular atrial fibrillation.
thanks HemOnc Today

Olanzapine for Break through nausea and vomiting

Anti-psychotic medication helps control breakthrough CINV

• Thanks HemOnc Today, July 10, 2012

CHICAGO — The anti-psychotic medication olanzapine helps to control breakthrough chemotherapy-induced nausea and vomiting that develops when patients do not respond to conventional prophylactic antiemetic treatments, according to results of a phase 3 trial.

Chemotherapy-induced nausea and vomiting (CINV) affects up to 90% of patients who undergo certain types of chemotherapy, according to background information provided by researchers. About one-third of those patients experience breakthrough CINV.

Olanzapine (Zyprexa, Eli Lily) has been shown to be safe and effective for the prevention of CINV. Researchers hypothesized that olanzapine also may be an effective rescue medication for patients who receive guideline-directed CINV prophylaxis but still experience nausea and vomiting.

Rudolph M. Navari, MD, PhD, clinical director of the Harper Cancer Institute at Indiana University School of Medicine-South Bend, and colleagues conducted a double-blind, randomized controlled trial to compare olanzapine to metoclopramide, which often is prescribed as a treatment for breakthrough CINV despite a lack of research proving its efficacy for that purpose.

Researchers enrolled 205 patients with a median age of 56 years who received guideline-recommended drugs to prevent CINV prior to undergoing their first round of chemotherapy. Eighty of those patients developed breakthrough CINV. Those patients then were randomly assigned to olanzapine 10 mg orally daily for 3 days (n=42) or metoclopramide 10 mg three times a day (n=28) for 3 days. Researchers followed the patients for 72 hours through phone calls from study nurses, and the patients also were asked to keep diaries of their experiences.

Thirty (71%) of the patients assigned to olanzapine experienced no vomiting, compared with 12 (32%) of the patients assigned to metoclopramide, a statistically significant difference. Sixty-seven percent of patients assigned to olanzapine reported experiencing no nausea, compared with 24% of patients assigned to metoclopramide, also a statistically significant difference.

Both treatments were well tolerated, researchers said.

Olanzapine, an FDA-approved treatment for psychosis, causes a variety of side effects when taken daily for 6 months or longer. However, no patients assigned to short-term treatment in this study reported grade-3/grade-4 toxicities, the researchers said.

Because breakthrough CINV typically develops between the second and fourth days after the start of chemotherapy, patients would not have to take olanzapine for longer than 3 days, Navari said in a press release.

“This is the first time that breakthrough CINV has been studied in a systematic way,” Navari said. “This study suggests that olanzapine will be very useful in these patients who feel very sick and sometimes come to the clinic, hospital or emergency room.”

FDA approves enzalutami​de to treat patients with metastatic castration​-resistant prostate cancer who previously received docetaxel

On August 31, 2012, the U. S. Food and Drug Administration approved enzalutamide (XTANDI® Capsules, Medivation, Inc. and Astellas Pharma US, Inc.), for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. 
The approval was based on a single randomized, placebo-controlled, multicenter trial enrolling 1199 patients with metastatic castration-resistant prostate cancer who had received prior docetaxel.  Patients were randomly allocated to receive enzalutamide 160 mg orally once daily (N = 800) or placebo (N = 399).  Study treatment continued until disease progression, initiation of new systemic antineoplastic treatment, unacceptable toxicity, or withdrawal.  Patients were required to continue androgen deprivation therapy and were allowed, but not required, to continue or initiate glucocorticoids during the study period.  Forty-eight percent (48%) of patients on enzalutamide and 46% on placebo received glucocorticoids. 
The primary efficacy endpoint was overall survival (OS).  At the pre-specified interim analysis after 520 events, a statistically significant improvement in OS [HR 0.63 (95% CI: 0.53, 0.75), p < 0.0001, log rank test] was observed.  The median OS was 18.4 and 13.6 months in the enzalutamide and placebo arms, respectively.
The most common (≥5%) grade 1-4 adverse reactions included asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension.  Grade 3-4 adverse reactions were reported in 47% of patients treated with enzalutamide and in 53% of those on placebo.
Seizures occurred in 0.9% of patients on enzalutamide.  No patients on the placebo arm experienced seizures.  In the clinical trial, patients experiencing a seizure were permanently discontinued from therapy.  All seizures resolved.  Patients with a history of seizure, taking medications known to decrease the seizure threshold, or with other risk factors for seizures were excluded from the clinical trial.  The safety of enzalutamide in patients with predisposing factors for seizures is unknown. 
The recommended dose and schedule for enzalutamide is 160 mg orally once daily.

New Treatment for Colon Cancer : ziv-aflibercept

On August 3, 2012, the U. S. Food and Drug Administration approved ziv-aflibercept injection (ZALTRAP®, Sanofi U.S., Inc.) for use in combination with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI) for the treatment of patients with metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin containing regimen.  Ziv-aflibercept (previously known as aflibercept) is a recombinant fusion protein consisting of vascular endothelial growth factor (VEGF)-binding portions from the extracellular domains of human VEGF receptors 1 and 2 that are fused to the Fc portion of the human IgG1 immunoglobulin.  

This approval is based on the results of a randomized, double-blind, placebo-controlled, global, multicenter trial enrolling patients with mCRC that progressed during or within 6 months of receiving oxaliplatin-based combination chemotherapy, with or without prior bevacizumab.

The Phase 3 trial accrued 1226 patients who were randomly allocated (1:1) to receive FOLFIRI (irinotecan 180 mg/m2 IV infusion over 90 minutes, leucovorin 400 mg/m² IV infusion over 2 hours, followed by 5-FU 400 mg/m² IV bolus, followed by 5-FU 2400 mg/m² continuous IV infusion over 46-hours) with either ziv-aflibercept (N=612) or placebo (N=614).  Ziv-aflibercept was administered at a dose of 4 mg/kg IV infusion over 1 hour prior to FOLFIRI.  The treatment cycles on both arms were repeated every 2 weeks.  Patients were treated until disease progression or unacceptable toxicity.  The primary efficacy endpoint was overall survival (OS).  Treatment assignment was stratified by the ECOG performance status and prior exposure to bevacizumab.

Median age of randomized patients was 61 years, 59% were men, and 98% had an ECOG performance status of 0 or 1.  All patients had received prior oxaliplatin treatment.  A statistically significant improvement in OS was observed in patients receiving FOLFIRI plus ziv-aflibercept compared to those receiving FOLFIRI plus placebo [HR 0.82 (95% CI: 0.71, 0.94), p=0.0032, stratified log-rank test].   The median OS was 13.5 and 12.06 months for patients on the ziv-aflibercept and placebo arms, respectively.  Median progression-free survival in the ziv-aflibercept arm was 6.9 compared to 4.7 months in the placebo arm [HR 0.76 (95% CI: 0.66, 0.87), p=0.00007]. 

The most common adverse reactions, (all grades), occurring in greater than or equal to 20%  of patients in the ziv-aflibercept plus FOLFIRI arm (with greater than or equal to 2% difference between arms) were leukopenia, diarrhea, neutropenia, proteinuria, increased AST and ALT, stomatitis, fatigue, thrombocytopenia, hypertension, decreased weight, decreased appetite, epistaxis, abdominal pain, dysphonia, increased serum creatinine, and headache.  The most common grade 3-4 adverse reactions (greater than or equal to 5%) reported at a higher incidence in the ziv-aflibercept plus FOLFIRI arm (greater than or equal to 2% difference between arms) were neutropenia, diarrhea, hypertension, leukopenia, stomatitis, fatigue, proteinuria, and asthenia. 

Severe and sometimes fatal hemorrhages, including gastrointestinal hemorrhages, have been reported in patients receiving ziv-aflibercept.   Grade 3-4 hemorrhagic events occurred in 2.9% of patients receiving FOLFIRI plus ziv-aflibercept compared with 1.7% of those receiving FOLFIRI plus placebo.  In addition to hemorrhage, the ziv-aflibercept label contains a Boxed Warning for the serious adverse reactions gastrointestinal perforation and compromised wound healing. 

Arterial thromboembolic events were observed in 1.7% and 2.6% of patients in the placebo and ziv-aflibercept containing arms, respectively.  Venous thromboembolic events were also observed more frequently with ziv-aflibercept:  9% patients in the ziv-aflibercept-containing arm compared to 7% in the placebo-containing arm.  Fistula formation and reversible posterior leukoencephalopathy syndrome have also been reported in patients who received ziv-aflibercept.

The recommended ziv-aflibercept dose and schedule is 4 mg/kg administered as a 60-minute IV infusion every 2 weeks in combination with the FOLFIRI regimen.

FDA Approves GSK Cancer Drug Votrient For Soft-Tissue Sarcoma

WASHINGTON (Dow Jones)--The Food and Drug Administration on Thursday approved GlaxoSmithKline PLC's (GSK, GSK.LN) cancer drug Votrient for use in patients with soft-tissue sarcoma, making it the first new treatment for the rare type of cancer in decades.

Votrient, a tablet taken orally, is already on the U.S. market to treat advanced kidney cancer. It was approved to treat several subtypes of advanced soft-tissue sarcoma, after prior chemotherapy. The disease starts in muscle or other connective tissues in the body.

The National Cancer Institute estimates there are about 11,000 cases of soft-tissue sarcomas diagnosed in the U.S. each year.

Votrient's approval follows the March recommendation of an agency advisory panel, which voted, 11-2, that the drug's benefits outweighed the risks. Clinical data involving 369 patients showed the drug temporarily slowed tumor growth.

Specifically, the study showed patients being treated with Votrient had a median progression-free survival of 4.6 months compared with 1.6 months on the placebo, or a difference of three months in the time before the cancer starts to worsen.

The FDA noted that Votrient carries the agency's toughest boxed warning, telling patients and health-care professionals about the potential risk of liver damage, which can be fatal. Patients should be monitored for liver function and treatment should be discontinued if liver function declines, the agency said.

The most common side effects seen in Votrient-treated patients were fatigue, diarrhea, nausea, weight loss, high blood pressure, decreased appetite, vomiting, tumor and muscle pain, hair color changes, headache, a distorted sense of taste, shortness of breath, and skin discoloration, the FDA said.

Thanks WSJ

TT

AAP now recommends HPV (Human Papilloma Virus) vaccine for boys and girls

The American Academy of Pediatrics Committee on Infectious Diseases issued an updated policy statement on human papillomavirus vaccination that recommends both boys and girls be immunized.

The policy statement notes vaccination reduces the incidence of sexually transmitted infections and reduces cancer risk.

ancers of the mouth and pharynx, which are increasing in recent years, and of anal and penile cancers.”

There currently is one approved HPV vaccine (HPV4; Gardasil, Merck) for boys and two vaccines — HPV4 and HPV2 (Cervarix, GlaxoSmithKline) — approved for girls.

The committee recommended that:

• Girls aged 11 to 12 years should receive three doses of HPV2 or HPV4 — administered intramuscularly at 0, 1 to 2, and 6 months — even if they already are sexually active.
• Boys aged 11 to 12 years should receive three doses of HPV4 using the same schedule.
• Females aged 13 to 26 years and males aged 13 to 21 years who were not previously immunized or who are missing a vaccination should complete the full series.
• Men aged 22 to 26 years who were not immunized previously or who are missing a vaccination may receive the HPV4 series, but “cost-efficacy models do not justify a stronger recommendation in this age group.”

The policy statement recommended that women who receive the vaccine continue to undergo cervical cancer screening.

About 20 million Americans currently have an HPV infection, and an estimated 7,080 men and 14,720 women develop cancers associated with HPV types 16 and 18 every year, according to the CDC.

An estimated 80% of anal cancers, 65% of vaginal cancers, 50% of vulvar cancers, 35% of penile cancers and nearly all cervical cancers are HPV-related. Roughly 60% of oropharyngeal cancers are associated with HPV.

thanks hemonctoday.com

Tony Talebi, MD

Chemotherapy for Metastatic Colon Cancer

CHEMOTHERAPY FOR UNRESECTABLE COLORECTAL CANCER:

As noted above, surgery is the only way to cure metastatic colorectal cancer. In most cases, surgery is not possible, and chemotherapy is recommended to reduce symptoms and prolong survival. Although chemotherapy provides meaningful improvements in survival, it is not possible to cure metastatic colorectal cancer with chemotherapy alone.

Continuum of care concept — With most types of incurable cancer (other than metastatic colorectal cancer), individual chemotherapy drugs or regimens are given continuously until the cancer stops responding to that drug or regimen, and then an entirely new regimen (termed "second-line therapy") may be tried.

The situation is different with metastatic colorectal cancer because there are many active drugs that can be combined in a number of ways. In addition, treatment-related side effects may be lessened by limiting the number of doses of certain drugs. Thus, instead of giving the first-line regimen until the tumor progresses, treatment is often individualized.

• Specific chemotherapy drugs may be given, stopped, and then restarted at a later time, sometimes in combination with other chemotherapy drugs.
• Periods of aggressive chemotherapy may be interspersed with periods of "maintenance" chemotherapy, allowing the patient to have the greatest possible quality of life while minimizing side effects.

This has been referred to as the "continuum of care" approach to treatment of metastatic colorectal cancer.

Conventional chemotherapy — The conventional chemotherapy drugs used to treat metastatic colorectal cancer include:

• 5-fluorouracil (abbreviated FU), which is usually given into the vein with a second drug called leucovorin, which enhances its activity
• Orally active FU-like drugs, such as capecitabine (Xeloda®)
• Oxaliplatin (Eloxatin®), which is given intravenously
• Irinotecan (Camptosar®), also given intravenously

These drugs work by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are less affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract. Effects of chemotherapy on these and other normal tissues cause side effects during treatment.

Targeted chemotherapy — Three other drugs that are active against metastatic colorectal cancer work by a different mechanism. These are referred to as "targeted chemotherapy agents" since they are antibodies (a type of protein) that work to inhibit a specific protein that is important for the growth and/or survival of colon cancer cells.

Because targeted chemotherapy does not directly interfere with rapidly dividing cells, they do not have the usual side effects of conventional chemotherapy. However, targeted chemotherapy has other unique side effects, which are described in detail below.

Currently available targeted chemotherapy includes:

Bevacizumab (Avastin®) — Bevacizumab binds to a protein called vascular endothelial growth factor (VEGF). VEGF is involved in the development of a blood supply within a growing cancer; this blood supply is essential for the tumor to grow and spread. Bevacizumab enhances the antitumor effect of other chemotherapy drugs. Bevacizumab is not effective when given by itself, but is generally given in combination with other drugs, such as oxaliplatin and irinotecan 

Cetuximab (Erbitux®) — Cetuximab targets a different protein, the epidermal growth factor receptor (EGFR), which is found in about 80 percent of colorectal cancers. Erbitux® is effective even if EGFR is not found in an individual tumor.

Cetuximab does not work for all patients. It depends on whether or not the tumor has a specific abnormality (a mutation in a gene called K-ras).

• If the tumor has a K-ras mutation, cetuximab does not work.
• If the tumor does not have a K-ras mutation, cetuximab does work (ie, it is effective).

Unlike bevacizumab, cetuximab is active when given alone or in combination with other drugs, like irinotecan.

Panitumumab (Vectibix®) — Like cetuximab, panitumumab also targets the EGFR. Like cetuximab, it is effective only for tumors that do not have a specific mutation in the K-ras gene.

Monitoring during treatment — A person's response to chemotherapy is monitored with periodic X-ray studies (such as CT scans) every six to eight weeks during therapy. In addition, blood levels of a tumor marker called carcinoembryonic antigen (CEA) are generally measured every one to three months during therapy. CEA levels are typically high in people with advanced colorectal cancer; persistently rising CEA levels suggest that disease is progressing and a change in therapy is warranted.

However, a rising CEA alone is not sufficient evidence to prompt a change in treatment. Disease progression should be confirmed with radiographic testing (eg, CT scan) or a biopsy before changing treatment.

Thanks uptodate.com

Tony Talebi, MD

Blinatumomab Produced Complete Remission in Pre B cell ALL

Blinatumomab, an investigational drug from a novel class known as BiTE antibodies, resulted in complete remission (CR) or complete remission with only partial hematologic recovery (CR+) in 9 of 12 patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL) in a small study.
Max Topp, MD, from the University Hospital of Wuerzburg, Germany, presented the interim results in a poster here at the 16th Congress of the European Hematology Association (EHA).
Blinatumomab appears to represent a new treatment option for patients with treatment-refractory ALL, he noted. "This is the first clinical evidence that this technology might provide the fifth pillar of cancer therapy. We are testing it in the most aggressive B-cell malignancy we know," he told Medscape Medical News in an interview.

The primary end point of the single-group, multicenter, exploratory phase 2 trial was the rate of CR or CR+. Secondary end points were toxicity and duration of response.

"Based on the results from the first 12 patients, there is reasonable hope that this will change the way we think about this disease," said Dr. Topp.
A previous phase 2 trial with blinatumomab, presented at the 2010 American Society of Hematology annual meeting, reported results from ALL patients who showed minimal residual disease (MRD) or leukemic cells in the bone marrow, despite having received chemotherapy. Results of this previous study showed that 80% (16 of 20) achieved MRD-negativity, all within the first treatment cycle. Disease-free survival was 60% after a follow-up of up to 27.5 months.
Dismal Prognosis for Relapsed/Refractory ALL
Blinatumomab is the first of a new class of agents designed to direct cytotoxic T-cells to CD19-expressing cancer cells. CD19 is a protein expressed on the surface of B-cell-derived ALLs and non-Hodgkin's lymphomas.
According to Dr. Topp, patients with refractory ALL have a dismal prognosis. Complete remission rates in this subset range from 17% to 45% with intensive chemotherapy, and treatment-related mortality rates range from 12% to 23%. "Even with the best chemotherapy currently available for these patients, such as FLAG/IDA [fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin], only 30% of patients will go into remission. Remission is then usually only of short duration, with a median of around 6 months," he explained.
In the current study, patients had difficult-to-treat B-precursor ALL, and all had relapsed after induction and consolidation therapy once or twice, or had refractory disease. The majority of patients had undergone allogeneic stem cell transplantation in addition to other chemotherapy.
After receiving blinatumomab, 9 of 12 patients reached the primary end point of CR or CR+; all 9 also reached the secondary end point of becoming MRD-negative or obtained molecular remission. Both CR and MRD were reached within the first cycle in responders, so it is "a precise and quick therapy," said Dr. Topp.
"This is unusual in this particular patient group," he remarked.
"This means there was a reduction in tumor burden of greater than 5 logs. This is very significant because the CR rate means a reduction of 1 log, but molecular remission equates to a reduction of 5 logs of tumor burden," he added.
The duration of response remains unknown in this particular trial, and will be reported at a later date, Dr. Topp noted. However, he cited a study he was involved with that was published online May 16 in the Journal of Clinical Oncology, which investigated the effect of blinatumomab on MRD and duration of response. "We found patients who are still MRD-negative after 2.5 years. Extrapolating from those data to this trial, there may be patients who experience a very similar clinical course," said Dr. Topp.


Very interesting Phase II trial for Pre B ALL which is a very difficult disease to treat.
Tony Talebi, MD

Researchers develop possible platelet production system

53rd ASH Annual Meeting

SAN DIEGO — Researchers from Japan have developed an immortalized megakaryocyte cell line derived from human pluripotent stem cells that could be used for a platelet production system, according to a presentation here.

“This is an exciting development for the transfusion community, as our methodology has proven that platelets can be created in the lab from human induced pluripotent stem cells,” researcher Koji Eto, MD, PhD, professor at the Center for iPS Cell Research and Application at Kyoto University in Japan, said in a press release. “The next step will be to conduct a trial to determine whether our platelets can function in the human body and potentially provide a stable supply of platelets at a predefined quality and quantity that can then be used for transfusion therapy.”

The researchers previously demonstrated that peak activation of the c-Myc gene in megakaryocyte progenitor cells, followed by a reduction of c-Myc expression, are key components of in vitro platelet generation. They also found that c-Myc overexpression increased the number of megakaryocytes and induced apoptosis and cell senescence.

In this study, they showed that this phenomenon is regulated by induction of the INK4a and ARF genes. They analyzed the effects of three scenarios: c-Myc and p53 knockdown, c-Myc and bcl-xL overexpression and c-Myc and BMI1 overexpression. They found that only c-Myc and BMI1 overexpression increased numbers of CD41a+/CD42b+ non-polyploid megakaryocytes for more than 3 months.

Thanks Hemonctoday.com

Tony Talebi, MD

Vemurafenib induced responses in previously treated metastatic melanoma Sosman JA. N Engl J Med. 2012;366:707-714.

The BRAF inhibitor vemurafenib induced clinical responses in more than half of patients with previously treated V600–mutant metastatic melanoma, according to study results published in The New England Journal of Medicine.

Based on earlier phase 1 trials indicating that vemurafenib (Zelboraf, Hoffmann-La Roche) produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma, researchers designed a multicenter, phase 2 trial to investigate the efficacy of vemurafenib with respect to overall response rate, duration of response and OS.

The study enrolled 132 patients who received oral vemurafenib 960 mg twice daily until the disease progressed or unacceptable toxic effects developed. Patients with disease progression were permitted to continue treatment if the investigator determined that the patient would benefit clinically.

According to study results, 53% of patients exhibited a confirmed overall response (95% CI, 44-62), with 6% exhibiting a complete response and 47% exhibiting a partial response. The median duration of response was 6.7 months (95% CI, 5.6-8.6), and the median PFS was 6.8 months (95% CI, 5.6-8.1). The median OS was 15.9 months (95% CI, 11.6-18.3).

“This study shows that [vemurafenib] changes the natural history of this disease,” researcher Antoni Ribas, MD, PhD, of UCLA’s Jonsson Comprehensive Cancer Center, said in a press release. “This data is beyond what I would have expected. We’re seeing a significant number of patients with durable responses to the drug, and that the whole group of treated patients is living longer. These results tell us that this drug is having a very big impact, and this changes the way we treat metastatic melanoma.”

The most common adverse events included alopecia, fatigue, grade-1 or -2 arthralgia, rash and photosensitivity. Cutaneous squamous cell carcinomas were diagnosed in 26% of patients.

“While the problem of relapse and resistance is great, this study provides evidence that, in some patients, their melanoma is controlled for over 2 years on the medication,” researcher Jeffrey A. Sosman, MD, of the Vanderbilt-Ingram Cancer Center, said in a press release.

Thanks hemonctoday

Tony Talebi, MD

ACIP recommends routine HPV vaccination for 11- to 12-year-old boys

The CDC's Advisory Committee on Immunization Practices today approved routine recommendation in favor of administering the quadrivalent HPV vaccine for boys aged 11 to 12 years.

Committee members decided that the vaccine (Gardasil, Merck) was safe, efficacious and cost-effective enough to warrant routine usage in this population. The recommendation issued in 2009 was permissive, meaning providers could give the vaccine to boys, but it was not routinely administered. This change would put the HPV vaccine into the regular vaccination schedule. The three-vaccination series can start as early as age 9 years.

"The committee recommended that routine vaccination of males aged 11 or 12 years with three doses of quadrivalent vaccine be given to prevent HPV infection and HPV-related disease," Anne Schuchat, MD,director of the CDC's National Center for Immunization and Respiratory Diseases, said in a phone call with reporters. "Boys and young men 13 to 21 years of age who have not already received the vaccine should be vaccinated."

Anne Schuchat, MD

Insurance companies typically cover HPV vaccine in boys, but that is not necessarily the case for a permissive recommendation, according to Schuchat, who said a routine recommendation for a vaccine usually translates into coverage without co-pays.

The committee voted 8-5 with one abstention in favor of recommending vaccination for young men up to age 21 years with permissive recommendation for men aged 22 to 26 years. The committee considered recommending vaccination up to age 26 years, which would have harmonized recommendations for men and women, but concluded that the vaccine was not cost-effective in men aged older than 21 years.

According to the committee, in extending the quadrivalent vaccine to young men, the vaccine was 89% effective against genital warts and 75% effective against precancerous anal intraepithelial neoplasia. Schuchat said the number of girls receiving vaccinations has been disappointing, and there is hope that vaccinating boys will protect both young women and young men.

Thanks hemonctoday.com

Tony Talebi, MD

Breast Cancer Drug Pertuzumab Gets FDA Priority Review

U.S. health regulators have granted a priority review for Roche Holding AG's (ROG.VX) experimental breast cancer drug pertuzumab, opening the way for a launch as early as 2012 for a product the Swiss company hopes can contain damage from lost sales when top seller Herceptin loses patent protection in a few years' time.
The U.S. Food and Drug Administration gave priority review status to the medicine, a humanized monoclonal antibody, after clinical trials using breast cancer patients showed it added six months to the time before their disease worsened. Breast cancer is the most common cancer among women worldwide.
Patients in the Phase III CLEOPATRA study who received pertuzumab in combination with Herceptin - another Roche breast cancer drug - and a chemotherapy agent called docetaxel lived for an average of 18.5 months without their tumors growing. That compared with 12.4 months for those who got only Herceptin and docetaxel.
People who received the combination also experienced a 38% reduction in the risk of their disease worsening or death.


This new Anti-Her therapy coupled with mTOR inhibitors are both very promising news for breast cancer patients.

Tony Talebi, MD

FDA approves first drug for metastatic basal cell carcinoma

The FDA today approved vismodegib for the treatment of adults with basal cell carcinoma.

The FDA approval, granted under the agency’s priority review program, allows vismodegib (Erivedge, Genentech) to be used by adults with locally advanced basal cell carcinoma who cannot be treated with radiation or surgery, or those whose disease has spread to other parts of the body.

Vismodegib is the first FDA-approved drug for metastatic basal cell carcinoma, the most common form of skin cancer. Vismodegib — taken once a day — inhibits the Hedgehog pathway, which is active in most basal cell cancers.

“Our understanding of molecular pathways involved in cancer, such as the hedgehog pathway, has enabled the development of targeted drugs for specific diseases,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “This approach is becoming more common and will potentially allow cancer drugs to be developed more quickly. This is important for patients who will have access to more effective therapies with potentially fewer side effects.”

Thanks hemonctoday.com

This is a very large milestone in the treatment of this very common malignancy.

Tony Talebi, MD

Oncotype DX Colon Cancer Test Changes Treatment in Close to One-Third of Patients

A survey of oncologists suggests that the Oncotype DX colon cancer test changes treatment recommendations for 29 percent of patients with Stage II colon cancer. These results will be presented at the 2012 Gastrointestinal Cancers Symposium.

This test is usually used for patients with lymph node negative breast cancer.

Gene expression profiling explores the patterns of genes that are active in tumor cells. Studies suggest that gene expression may provide important information about prognosis or likely response to treatment in several types of cancer. For example, among selected women with early-stage breast cancer, the Oncotype DX breast cancer test has been shown to predict the likelihood of cancer recurrence and the likelihood of benefit from chemotherapy. As a result, the test has been added to medical guidelines for early-stage breast cancer.

A similar test became available for patients with Stage II colon cancer in 2010. Stage II colon cancer refers to cancer that extends through the wall of the colon but has not invaded lymph nodes or spread to distant parts of the body. Many patients with this stage of disease have good outcomes with surgery alone, and routine adjuvant (post-surgery) chemotherapy is not currently recommended for Stage II colon cancer. Chemotherapy may, however, be considered for Stage II patients with a higher risk of cancer recurrence.

Thanks cancerconnect.com

This will be a great tool for patients with stage II colon cancer and will make the decision to administer adjuvant chemotherapy or not easier.

Tony Talebi, MD

FDA approves axitinib for Kidney Cancer (renal cell carcinoma)

he FDA today approved axitinib tablets for use in patients with previously treated advanced renal cell carcinoma.

The FDA approved Axitinib (Inlyta, Pfizer) based on a single international, randomized, open-label trial involving patients with advanced renal cell carcinoma after failure of one prior systemic regimen.

Researchers evaluated 723 patients who were randomly assigned to receive axitinib 5 mg orally twice daily (n=361) or sorafenib 400 mg orally twice daily (n=362). Patients continued in their treatment until disease progression, the point of unacceptable toxicity or consent withdrawal. Enrollment criteria included an ECOG performance status of 0 or 1 and at least one prior systemic therapy that consisted one of the following treatments: sunitinib, temsirolimus, bevacizumab or cytokine(s).

Patients in the axitinib group demonstrated significantly extended PFS (HR=0.67; 95% CI, 0.54-0.81,P<.0001), with a median PFS of 6.7 months (95% CI, 6.3-8.6) compared with 4.7 months (95% CI, 4.6-5.6) for patients in the sorafenib group. That represented a 43% improvement in median PFS compared with sorafenib.

The most common adverse reactions (≥20% of patients) in the axitinib-treated group were diarrhea, diminished appetite, hypertension, fatigue, constipation, palmar-plantar erythrodysesthesia syndrome, nausea, dysphonia, weight loss, vomiting and asthenia. Other severe adverse reactions reported were hypertensive crisis, hemorrhage, gastrointestinal perforation and fistula formation, arterial and venous thrombotic events, and reversible posterior leukoencephalopathy syndrome.

Thanks hemonctoday.com

This gives us even more weapons to utilize in our growing armamentarium against metastatic renal cell cancer.

Tony Talebi, MD

Study: Obesity increases risk of esophageal and gastric adenocarcinoma

Obesity may be linked to an increased risk of esophageal and gastric adenocarcinoma, according to a large prospective cohort study.

BMI was associated with a higher risk of esophageal and gastric cardia adenocarcinoma. Abdominal obesity — measured by waist size and waist-to-hip ratio — was associated with increased risk of esophageal cancer.

The study cohort included 218,854 subjects from the NIH–AARP Diet and Health Study, conducted in 1995 and 1996.

Investigators found that waist circumference alone was related to an increased risk of gastric cardia adenocarcinoma. They also found that in patients with normal BMI (18.5 <Kg/m?), a positive association persisted between waist-to-hip ratio and esophageal adenocarcinoma.

Obesity is the single most important problem facing first world as well as developing nations as decreased human activity coupled with increased calorie intake is causing an epidemic wave of children and adults.

Not only does obesity lead to diabetes, cardiovascular complications, and strokes but also many cancers such as breast cancer, prostate cancer, colon cancer and gastric as well as esophageal cancer.

In my opinion, children need to exercise much more and eat a healthier diet.   Restaurants need to be required by law to disclose the calorie content of every single meal on the menu, and insurance companies should pay for personal trainers and cooks for those who need to change their lifestyle drastically for at least a period of 6 months.

Tony Talebi, MD

IP cisplatin, early start of chemotherapy associated with improved efficacy of iceMFP chemotherapy

2012 Gastrointestinal Cancers Symposium

SAN FRANCISCO — Phase 3 results from the AMC 0101 study showed patients treated with iceMFP chemotherapy for serosa-positive advanced gastric cancer had superior outcomes when assigned to intraperitoneal cisplatin and/or early start of chemotherapy.

Patients were assigned to Mf (20 mg/m² of mitomycin-C and daily oral 460-600 mg/m² doxifluridine) or iceMFP (mitomycin-C and doxifluridine plus cisplatin). Patients received 100 mg intraperitoneal cisplatin for two hours during surgery, and 15 mg/m² IV mitomycin-C one day after surgery. Doxifluridine was administered 4 weeks after surgery for a total of 12 months, along with six shots of monthly 60 mg/m²cisplatin.

As of April 2011, a median follow-up of 6.6 years, patients assigned to iceMFP demonstrated superior 5-year recurrence-free survival (HR=0.73; 95% C.I. 0.57-0.93) and 5-year OS (HR=0.77; 95% C.I. 0.60-0.98) compared with patients assigned to Mf chemotherapy.

That represented a 9% improvement in OS compared with 3-year results, said Yoon-Koo Kang, MD, PhD,with the Asan Medical Center in Seoul, South Korea.

I have always wondered if intraperitoneal chemotherapy could improve survival in gastric cancer since the cancer cells are often in the peritoneal cavity.

We will have to see our own trials in the USA.

Tony Talebi, MD

FDA approves glucarpidase injection for treatment of toxic plasma methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function

On January 17, 2012, the U. S. Food and Drug Administration approved glucarpidase  injection (Voraxaze®, BTG International Inc.) for the treatment of toxic plasma methotrexate concentrations (> 1 μmol/L) in patients with delayed methotrexate clearance due to impaired renal function.* 

The approval was based on the pharmacodynamic endpoint of a rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, defined as an attainment of plasma methotrexate concentration less than or equal to 1 μmol/L within 15 minutes following glucarpidase administration and sustained for up to 8 days.

Efficacy was established in 22 patients with delayed methotrexate clearance (more than 2 standard deviations above the average indicated on standard nomograms) secondary to renal dysfunction.  The efficacy assessment was limited to patients having pre- and post-treatment plasma samples collected and handled according to a validated procedure to yield reliable methotrexate measurements by HPLC.

All patients received glucarpidase, 50 Units/kg, as an intravenous injection over 5 minutes. Patients with pre-glucarpidase methotrexate concentrations >100 μmol/ L were to receive a second dose of glucarpidase 48 hours after the initial dose.  All patients received vigorous intravenous hydration, urinary alkalinization, and leucovorin rescue. 


Thanks ASCO.org


Tony Talebi, MD

What You Should Know about Denosumab (Prolia) for Increasing Bone Mass during Breast and Prostate Cancer Therapies

In September 2011, the monoclonal antibody RANKL inhibitor denosumab (Prolia) was approved for use in increasing bone mass in patients at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer or aromatase inhibitor therapy for breast cancer.¹ Under the trade name Xgeva, denosumab has an indication for prevention of skeletal-related events in patients with bone metastases from solid tumors at a different dose (120 mg subcutaneously every 4 weeks) than in the current indications. Denosumab (as Prolia) also has a nononcologic indication for treatment of postmenopausal women with osteoporosis at high risk for fracture.


Visit ASCOPOST.ORG

Tony Talebi, MD

FDA approves Bristol's Yervoy (ipilimumab) for melanoma

This is also a ground breaking event in the history of melanoma treatment for our patients.

The FDA has approved Yervoy (ipilimumab), a closely-watched new drug for advanced melanoma. 

The drug approval is a rare win in the field of melanoma, which has experienced more than its fair share of new drug failures. Melanoma that has spread to other organs is notoriously difficult to treat, leaving patients with few options. Researchers observed higher one- and two-year survival rates for patients on Yervoy, and although ipilimumab is linked to some severe side effects--including colon inflammation, diarrhea and skin rashes and even death--the dearth of options for advanced-stage melanoma patients prompted the agency to approve the drug.

Tony Talebi, MD

Bevacizumab delayed progression of epithelial ovarian cancer

The use of bevacizumab during and after carboplatin and paclitaxel chemotherapy prolonged progression free survival (meaning delay in progression) in patients with epithelial ovarian cancer by approximately 4 months, according to trial data published in the Dec. 29 issue of The New England Journal of Medicine (the gold standard Journal for physicians).

In a double blind, placebo-controlled, phase 3 trial (the most accurate trials that doctors pay attention to), 1,873 patients were enrolled from 336 sites in the United States, Canada, South Korea and Japan. Researchers randomly assigned eligible patients — eligibility determined as previously untreated or incompletely resectable stage III or any stage IV ovarian cancer.

At the conclusion of the study, patients who received bevacizumab with chemotherapy throughout demonstrated a longer median of progression free survival (14.1 months) compared with patients in the control group (10.3 months) and the bevacizumab/placebo group (11.2 months).

This is certainly an option which may be entertained in patients with metastatic ovarian cancer.

Tony Talebi, MD

This could be the biggest deal in colon cancer

Hi,

This is tremendous news for metastatic colon cancer patients.   The trial was actually stopped early since the data was in such favor for patients who were being treated with this new drug called Regorafenib.

Tony Talebi, MD

Phase III Trial of Regorafenib in Metastatic Colorectal Cancer Meets Primary Endpoint of Improving Overall Survival

Trial stopped based on positive data from a pre-planned interim analysis

Berlin, October 26, 2011 – Bayer HealthCare today announced positive results from its Phase III trial evaluating its investigational compound regorafenib (BAY 73-4506) for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed after approved standard therapies: The trial met its primary endpoint of statistically significantly improving overall survival. This is the result of a pre-planned interim analysis conducted by an independent Data Monitoring Committee (DMC) of the CORRECT (Patients with metastatic colorectal cancer treated with regorafenib or placebo after failure of standard therapy) trial. Per the recommendation of the DMC, the study has been unblinded and patients in the placebo arm will be offered treatment with regorafenib. In this trial, the safety and tolerability of regorafenib were generally as expected and did not show any new or unexpected toxicities. Data from the study are expected to be presented at a forthcoming scientific meeting. 

“These data are significant because they demonstrate that regorafenib increases overall survival in patients with heavily pretreated mCRC, an area of high unmet medical need,” said Kemal Malik, MD, Head of Global Development and member of the Bayer HealthCare Executive Committee. “We are extremely encouraged by the result of this analysis and we are hopeful about the potential of regorafenib to fill this unmet treatment need.”

Bayer will continue discussions with health authorities worldwide, including the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) regarding next steps in filing for approval of regorafenib in the treatment of mCRC.

Bayer recently entered into an agreement with Onyx Pharmaceuticals, Inc. under which Onyx will receive a royalty on any future global net sales of regorafenib in oncology.

About the CORRECT Study 
The CORRECT trial is an international, multicenter, randomized, double-blind, placebo-controlled study that enrolled 760 patients with mCRC whose disease has progressed after approved standard therapies. The study was conducted in North America, Europe, China, Japan and Australia.

Patients were randomized to receive either regorafenib plus best supportive care (BSC) or placebo plus BSC. Treatment cycles consisted of 160 mg of regorafenib (or matching placebo) once daily for three weeks on / one week off plus BSC. The primary endpoint of this trial was overall survival. Secondary endpoints included progression-free survival, objective tumor response rate and disease control rate. The safety and tolerability of the two treatment groups were also compared.

About Colorectal Cancer
Colorectal cancer (CRC) is a disease in which malignant (cancer) cells form in the tissues of the colon or rectum. The majority of cancers occurring in the colon and rectum are adenocarcinomas, which account for more than 90 percent of all large bowel tumors. 

CRC is the fourth most common cancer worldwide, with over one million cases occurring every year. The mortality rate from CRC is approximately half of its global incidence. The five-year survival estimate for CRC on average is 55 percent, but varies very much dependent on the stage of the disease (from 74 percent for patients with Stage I disease to only 6 percent for Stage IV patients). 

About Regorafenib 
Regorafenib is an investigational oral multi-kinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases (TK). Regorafenib inhibits angiogenic kinases like receptors for VEGF which play central roles in angiogenesis. It also inhibits various oncogenic kinases including RAF, RET as well as stromal kinases such as KIT and PDGFR, thereby helping to stop the proliferation of cancer cells. Regorafenib has shown antitumor activity in preclinical studies by inhibiting tumor growth in multiple xenograft models via antiangiogenic and antiproliferative mechanisms. Based on these results, regorafenib is currently being investigated in clinical trials for its potential to treat patients with various tumor types. 

Regorafenib is an investigational agent and is not approved by the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA) or other health authorities.

Regorafenib was granted orphan drug designation by the FDA for the treatment of patients with gastrointestinal stromal tumors (GIST). Orphan drug designation aims to encourage the development of drugs involved in the diagnosis, prevention or treatment of a medical condition affecting fewer than 200,000 people in the country. 

Regorafenib was granted Fast Track designation by the U.S. FDA for the treatment of patients with metastatic and/or unresectable GIST whose disease has progressed despite at least imatinib and sunitinib as prior treatments, as well as for the treatment of patients with mCRC who have progressed after approved standard therapies. Fast Track is a process designed to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need.

About Oncology at Bayer
Bayer is committed to advancing the science of cancer, and translating this science into therapies that can help people with cancer live longer. With several potential first- and best-in-class compounds in clinical development, Bayer’s oncology portfolio demonstrates the Company’s commitment to improving the lives of people living with cancer. 

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 16.9 billion (2010), is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 55,700 employees (Dec 31, 2010) and is represented in more than 100 countries. Find more information at www.bayerhealthcare.com.

Find more information at www.bayerpharma.com.

We will await approval of this medicine in the USA

Tony Talebi, MD

hemonc101.com

www.HemOnc101.com at ASH

The HemOnc101 team wanted to thank everyone who stopped by our booth at ASH.
We enjoyed meeting people from all over the world.