Thirty years of randomized clinical studies point to the need for changes in our approach to the chemotherapy of the most common forms of adult cancers. Despite reportably doubling of response rates, there has been no hint of improved overall patient survival.
Experience in metastatic breast cancer is very informative and indicates this lack of improved overall patient survival. Back in the early 70s, the median survival for metastatic breast cancer was just under two years. Today it is precisely the same, just under two years. In scores of prospective randomized trials involving tens of thousands of patients, response rates have gone up. Some patients unquestionably have their lives prolonged by years. Yet the overall survival rates have not improved.
The reason may be because it's all a zero sum game. You give more aggressive chemotherapy in diseases like metastatic breast cancer and you increase response rates, but you don't improve overall survival. The true situation is not that either chemotherapy works or it doesn't. The true situation is that ineffective, aggressive chemotherapy can diminish not just quality of life but also quantity of life, through organ toxicity, immunosuppression, or by inducing mutations in genetically unstable tumor cells to make them more aggressive. The result is no improvement in the treatment of the most common forms of metastatic cancer over the past 30 years
What you may want to do is to reserve the 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 in general, the most promising treatments may include angiogenesis inhibitors, growth factor inhibitors, or more holistic therapy approaches.
It could be that a better approach for treating recurrent cancer is not to give more aggressive and toxic and mutagenic and immunosuppressive combinations, but to give targeted single agents, or to give the least toxic and mutagenic active combinations. Higher response rates don't necessarily lead to improved clinical outcomes.
The era of empiric, aggressive, multi-agent cytotoxic chemotherapy for recurrent/refractory adult solid tumors should come to an end. We should put much more emphasis on matching treatment to patient, through the use individualized testing, have more respect for minimal partial response or stable disease, when it can be achieved through the use of least toxic and mutagenic drug regimens, and reserve the use of higher dose therapy or agressive combination chemotherapy to those fortunate patients with tumor biologies most amenable to attack and be subjected to total or near-total destruction by these aggressive treatments.
The hallmark of cancer is heterogeneity. Not just many types of cancer (ovarian, breast, lung, colon, etc.), but many subtypes of cancer within a given type. Many types of ovarian cancer. Many types of breast cancer. Many types of lung cancer, etc. The biologies are very different and the response to given drugs is very different.
The hallmark of cancer treatment is heterogeneity. There are currently over 100 FDA approved cancer drugs, with hundreds more in the pipeline. All of these drugs tend to be partially effective, and even then, in only a minority of cases, and often for only a short duration of time.
The single most neglected area of cancer research has been the development of methods and technologies to be "matchmakers" between individual cancer with individual cancer treatment.
The single most neglected area of cancer treatment has been the unwillingness to utilize, or even study, the matchmaker technologies which have already been developed and which are already available. These technologies involve studies of cancer cell responses to drug exposure in cell culture systems, "outside" of the patient's body, before they are put "into" the patient's body.
One of the ways of matching the treatment to the patient is assay-testing. Not all patients will have the same response to the same chemotherapy. Special laboratories can test tumor samples from individual patients to see which chemotherapy drugs have the best likelihood of killing tumor cells and optimizing survival. The results provide medical and surgical oncologists with patient-specific tumor information that may provide additional insight when determing the appropriate course of treatment for a patient.
Assay-testing focuses on the unique characteristics of a particular cancer. The test results help the physician to determine which anti-cancer drugs are "likely" to be effective against a particular cancer. The assay test also helps the physician to determine which anti-cancer drugs are "unlikely" to affect a cancerous tumor, which can help to avoid toxic and possibly ineffective therapy.
The tests have a specifity (for drug resistance) of 0.92 and a sensitivity (for drug resistance) of 0.71, which means that a treatment regimen "not" resistant in the assays is 7-9 fold more likely to work than is a treatment regimen which "is" resistant in the assays. A preponderance of evidence would indicate that it would be worthwhile to consider the assay results in drug selection.
For more information about the technology of assay-testing:
http://www.positivehealth.com/test/articles.asp?i=1832