HPV Vaccine Not Effective for Treating Pre-Existing Infections
A vaccine developed to prevent infection with human papillomaviruses (HPV), the cause of cervical cancer, was found to be ineffective for treating women with pre-existing HPV infections, according to a study published in the August 15 Journal of the American Medical Association.
The study, a community-based, randomized trial of 2,189 women in Costa Rica, was conducted by NCI's Division of Cancer Epidemiology and Genetics (DCEG) and Costa Rican investigators. The researchers found no significant difference in how quickly an HPV infection was cleared among those who received the HPV vaccine compared with the control group who received vaccinations for hepatitis A. At the 6-month follow-up visit, rates of viral clearance were 33.4 percent for women who received vaccines against HPV types 16 and 18 compared with a 31.6 percent rate among the control group. At the 12-month visit, rates of clearance in the HPV vaccine group were 48.8 percent versus 49.8 percent for the controls.
"The main finding of the study was to demonstrate that among women who are already infected, the HPV vaccine does not help accelerate the rate of viral clearance," commented Dr. Allan Hildesheim with DCEG. "Therefore, women who are infected with HPV should not take the vaccine to treat their infections or associated lesions." The study reinforces the importance of targeting HPV vaccination towards adolescent girls before they begin sexual activity "because that would maximize the benefit provided by vaccination," he added.
The study is part of a larger community-based clinical trial of 7,466 Costa Rican women. The larger study will address broad issues about the vaccine including efficacy, duration of protection, and global impact of vaccination on HPV and HPV-related disease. Among other questions, "the study will address whether vaccination is important for women who have previously been infected and have cleared the infection by themselves," said Dr. Hildesheim.
Drug Combination Shows Benefit in Relapsed/Refractory Multiple Myeloma
Interim results from a phase III clinical trial suggest a new combination treatment should be another standard of care for patients with relapsed or refractory multiple myeloma, according to the trial's leaders.
In the most recent survival analysis from the 646-patient trial, released early online on August 6 in the Journal of Clinical Oncology, the combination of pegylated liposomal doxorubicin (Doxil) and bortezomib (Velcade) improved the median time to disease progression compared with bortezomib alone (9.3 months vs. 6.5 months) and yielded a superior 15-month overall survival rate (76 percent of patients in the combination group were alive at 15 months compared with 65 percent in the bortezomib-only group).
The results come 2 years after a phase III trial showed that bortezomib alone was superior to dexamethasone, another drug commonly used to treat all stages of multiple myeloma, and 1 year after a trial demonstrated that the combination of lenalidomide (Revlimid) and dexamethasone was superior to dexamethasone alone in patients with refractory or relapsed disease.
The bortezomib/Doxil combination also increased the duration of response, reported the study's principal investigator, Dr. Robert Z. Orlowski from the University of Texas M.D. Anderson Cancer Center, and colleagues. However, the combination's benefits came at the expense of an increased risk of adverse events, including high-grade hematologic (e.g., neutropenia) and gastrointestinal (e.g., diarrhea, nausea) toxicities.
Based on the results of this trial, also known as the DOXIL-MMY-3001 study, the U.S. Food and Drug Administration recently approved the use of this combination for treating patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.
Irinotecan Not Effective in Adjuvant Therapy for Colon Cancer
Final results from a Cancer and Leukemia Group B (CALGB) trial show that irinotecan should not be added to 5-fluorouracil (5-FU) and leucovorin in the adjuvant treatment of stage III colon cancer. In the CALGB 89803 trial, led by Dr. Leonard B. Saltz and colleagues at Memorial Sloan-Kettering Cancer Center, no survival benefit was seen in the adjuvant setting. These results appear in the August 10 Journal of Clinical Oncology.
"These results were unexpected," writes Dr. Neal Meropol of the Fox Chase Cancer Center in Philadelphia in a related editorial. "After all, CPT 11 [irinotecan] had previously shown clear activity in patients with metastatic cancer - the accepted proving ground for subsequent adjuvant therapies."
In previous trials, Dr. Saltz and others had found that adding irinotecan to 5-FU and leucovorin provided a modest but statistically significant improvement in survival compared to treatment with 5-FU and leucovorin alone in patients with metastatic colon cancer. Based on these findings, it was anticipated that the three-drug combination would also be effective when given after surgery to patients with less advanced disease.
"The report by Saltz et al. sends a strong message," said Meropol. "Randomized trials are necessary to prove the obvious, [because] history tells us that the obvious is often disproved."
Saltz and colleagues agreed. "The results of our trial demonstrate the dangers of jumping to conclusions before completion of the formal clinical trial assessment."In addition, combining irinotecan with 5-FU and leucovorin significantly increased treatment toxicity, including greater reductions in white blood cell counts and increases in infection, vomiting, and fatigue. More than 10 percent (65) of the 635 patients assigned to the irinotecan-containing arm had their treatment stopped because of an adverse event. Another 82 patients receiving the three-drug combination withdrew from the trial, more than twice the number of patients who withdrew from the 5-FU plus leucovorin arm. Within 60 days of entering the study, 14 patients receiving irinotecan died, compared to 5 in the 5-FU and leucovorin arm.