Monday, March 19, 2012

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.

Tony Talebi, MD

Sunday, March 11, 2012

Chemotherapy for Metastatic Colon 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.


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

Sunday, March 4, 2012

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.

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