What should I expect from Gemzar & Carboplat?

Clinical Oncologists for Individualized Treatment of cancer patients have found out years ago that the combination of gemcitabine + platinum (either cisplatin, carboplatin or oxaliplatin) was the most important drug combination introduced for the treatment of solid tumors in the past 18 years. Clinical responses with this regimen were unprecedented.

According to a study published in Gynecologic Oncology, the most probable mechanism for the synergy between gemcitabine + platinum is gemcitabine inhibition of repair of platinum/DNA adducts. What this means is that platinum-resistant tumor cells "cut out" the damaged DNA (to which the platinum is attached) in the same way that the railroad company repairs damaged sections of rail track. Then the railroad company lays down new track. Platinum-resistant tumor cells do the same thing, and gemcitabine interferes with this process.

Thus, you want to administer first gemcitabine (to have gemcitabine on board to inhibit the repair process). Then, you want to administer platinum shortly thereafter. In addition, you don't want to give either gemcitabine or platinum by itself on any days of the cycle; this doesn't take advantage of the synergy between the drugs and, in many cases, will just increase toxicity (Belpomme, et al. Gynecol. Oncol. 91:32-38, 2003).

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, and 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.

A myriad number of choices exist. Doxil, Etoposide, Gemcitabine (Gemzar), 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 patients derive benefit from gemcitabine + platinum administered 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 (Alimpta), ifosfamide + cyclophosphamide (plus or minus gemcitabine), Mitomycin c, and others. In ovarian cancer a greast many drugs can be and should be tested. Patients can be managed on the basis of information provided by cell culture assay tests.