Ovarian Cancer Patients Benefit from Dose-dense Therapy

[tealnews]

Ovarian Cancer Patients Benefit from Dose-dense Therapy

Women with advanced epithelial ovarian cancer survive longer with dose-dense treatments of paclitaxel compared to conventional regimens, according to results of a study published in The Lancet (2009;347[9698]:1331-1338).

In the press release announcing the findings, the authors explained that paclitaxel and carboplatin given every 3 weeks is currently considered standard first-line chemotherapy for advanced epithelial ovarian cancer. The authors also explained that dose-dense weekly administration of paclitaxel is another strategy to enhance antitumor activity and prolong survival.

For the study designed to compare a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer, Noriyuki Katsumata, MD, of the National Cancer Center Hospital in Tokyo, Japan, and colleagues recruited patients with advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Patients were assigned to 2 different groups; the conventional treatment group was given 6 cycles of paclitaxel plus carboplatin and the dose-dense treatment group was given 6 cycles of a dose-dense paclitaxel plus carboplatin.

The researchers found that median progression-free survival was longer in the dose-dense treatment group (28 months) than in the conventional treatment group (17 months). The data also revealed that at 3 years, the dose-dense regimen group had a higher rate of overall survival (72%) compared to the conventional treatment group (65%).

The authors say that the survival benefits shown in the dose-dense group are rare in women with advanced ovarian cancer. “Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer,” the authors concluded.

[gpawelski]

Despite scores of prospective randomized clinical trials, involving tens of thousands of patients with aggressive chemotherapy combinations and high dose regimens, the experience with metastatic cancer shows that response rates have gone up, but the overall survival rates have not improved. We relentlessly combine chemotherapy agents in various regimens with ever-increasing dose intensity.

The problem is that ineffective, aggressive chemotherapy can diminish not just the quality of life but also the quantity of life, through organ toxicity, immunosuppression, and inducing mutations in genetically unstable tumor cells to more aggressive phenotypes. The result is that there has not been any improvement in the treatment of the most common forms of metastatic cancer.

There appears to be a number of patients who have had long-term survival after high dose therapy, but there are a number of patients whose tumors are responsive to chemotherapy who have had long-term remissions from standard dose chemotherapy, as well as a number who show no difference in survival when treated with standard-dose or high-dose chemotherapy. Does chemotherapy shorten survival of some patients, while prolonging the survival of others?

You may want to reserve aggressive therapy for those patients who will derive more benefit than harm, while identifying the most promising treatment regimens for everyone. In patients with tumors very resistant to cytotoxic chemotherapy, the most promising treatments may be angiogenesis inhibitors, growth factor inhibitors, or more integrative medicine approaches.

It may be better not to give more aggressive and toxic, mutagenic and immunosuppressive combinations, but to give targeted single agents, or give least toxic, mutagenic synergistic combinations. One of the most important drug combinations introduced for the treatment of solid tumors in the last 15 years has been the gemcitabine + platinum combination. However, giving this combination to everyone would not be that helpful, because the immunosuppression and mutagenicity of the combination cancels out in many patients, the gains in a few, fortunate patients.

More emphasis should be put on matching treatment to the patient, through the use of individualized pre-testing, having more respect for minimal partial response or stable disease, when it can be achieved through use of the least toxic and mutagenic drug regimens, and reserve the use of higher dose therapy or aggressive combination chemotherapy to those patients with tumor biologies most amenable to attack and destroy by these aggressive treatments.

Sources:
Oncol News Int'l, Vol 14, #5, May '05
Cell Function Analysis