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High-dose chemo and stem cell transplant
In the 90's, we were subjected to bigger guns, more firepower with high dose chemotherapy and stem cell transplant, costing as much as $250,000. This tragedy was a watershed event for many advocates. More is not always better.
You give more aggressive chemotherapy (i.e. combinations, high dose therapy, whatever) in diseases like metastatic breast cancer 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, and/or by inducing mutations in genetically unstable tumor cells to more aggressive phenotypes.
You want 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, and/or more holistic ("integrative medicine") therapy approaches.
A myriad number of choices exist in the above situation: Doxil, etoposide, gemcitabine and gemcitabine-based combinations (including gemcitabine + platinum combinations). Gemcitabine circumvents tumor cell resistance to platinum in some cases by preventing the tumor cells from repairing platinum-induced DNA damage.
But not all (or even most) patients derive benefit from gemcitabine + platinum administration on an empiric basis, because it only works against some tumors (but when it works, it often works very well). Additional possibilities are melphalan, hexamethylmelamine, 5FU (including Xeloda), oxaliplatin, gemcitabine + oxaliplatin, vinorelbine + oxaliplatin, gefitinib (Iressa), pemetrexed (Alimta, very recently FDA-approved for mesothelioma, but can be given to patients with ovarian cancer), ifosfamide + cyclophosphamide (minus or plus gemcitabine), mitomycin c, and so forth.
There is no proven "standard" first line therapy which has been shown to be superior to the many other choices which exist. The same situation exists in the setting of 2nd, 3rd, 4th line therapy. The therapies are equivalent on a population basis, but not on an individual basis. Proven by the large number of patients who have progressive disease on 1st line therapy but who have good responses to 2nd or 3rd line therapy. These patients should have received the "correct" treatment in the first line setting.
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