Only a few years ago it was still a debate, whether patients with advanced colorectal cancer should be treated by a palliative chemotherapy at all. After the demonstration of a palliative benefit of these patients in terms of prolongation of time to progression, survival and improvement of quality of life by first-line chemotherapy, now also several second-line chemotherapy options are available. However, due to the nature of early phase II studies and in the absence of prospective randomized trials comparing the different available salvage treatment options, a clear definition of the optimal salvage treatment strategy and sequence is very difficult. The evaluation of currently available data of controlled clinical trials allows at least a suggestion what should be done in case of progression under or after a bolus 5-FU/Folinic Acid (FA) protocol. The following recommendations should help to define the suitable protocol for every patient although it should be mandatory to treat patients within ongoing comparative clinical trials: In case of progression after a treatment-free intervall of 3 months from the end of the first-line (or prior) 5FU +/- FA-based chemotherapy and prior response (partial response or minor response), the patient should be retreated with the same regimen. -In case of progression under retreatment or shortly after a first-line 5-FU/FA treatment, the further treatment options depend on the prior treatment: in case of 5-FU given as a bolus or short infusion while prior treatment the salvage protocol should use any type of protracted 5-FU-infusion +/- FA, e.g., 5-FU daily continuously until progression or weekly 24-hours infusion of 5-FU/FA. An alternative is CPT-11 (Irinotecan) as single agent, which is more easy to apply but more toxic (particularly bone marrow toxicity, diarrhea and alopecia) -in case of pretreatment with 5-FU given as prolonged high-dose infusion, one could proceed with the same infusional 5-FU regimen including the addition of Oxaliplatin; this protocol could be given weekly or biweekly (FOLFOX-2 protocol) or for 5 days with chronomodulation of 5-FU every 3 weeks. The alternative would be CPT-11 as single agent every 3 weeks; this protocol avoids the neurotoxicity which appears after higher cumulative dose of Oxaliplatin, but is associated with bone marrow toxicity, diarrhea and alopecia. In case of progression after infusional high-dose 5-FU/FA plus Oxaliplatin and no prior exposure to CPT-11, this agent is the last available option; however, it is not clear whether CPT-11 has relevant efficacy in patients refractory to infusional 5-FU plus Oxaliplatin.If the bulk of the disease is located in the liver, besides all the above mentioned options one should always consider locoregional treatment via hepatic artery (by femoral catheterization).

Keywords:
Colorectal cancer, Second-line chemotherapy, Salvage treatment, Palliative treatment
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© 1997 S. Karger AG, Basel
1997
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