Dramatic tumor response of bulky liver metastases following treatment withCPT-11 and a chronomodulated 4-day infusion of 5-fluorouracil, folinic acid and oxaliplatin every 2 weeks in a colorectal cancer patient

Three active antitumor agents, i.e. 5-fluorouracil (5-FU), oxaliplatin and CPT-11, are available for the treatment of advanced colorectal cancer (CRC) patients and have been successfully combined in two-drug regimens. Hence, CRC has become a chemosensitive disease, but the optimal combination of the se agents in first-line treatment remains to be determined. We report the f irst case of the combination of CPT-11 with oxaliplatin, 5-FU and folinic a cid (FA) as first-line chemotherapy for a patient with a pre-occlusive sigm oid adenocarcinoma and synchronous bulky liver metastases. CPT-11 was given at 125 mg/m(2), prior to the start of a chronomodulated 4-day infusion of oxaliplatin 25 mg/m(2)/day, 5-FU 800 mg/m(2)/day and FA 300 mg/m(2)/day rep eated every 2 weeks. The doses could be escalated to 150 mg/m(2) for CPT-11 and 900 mg/m(2)/day for 5-FU, After six cycles of chemotherapy 70% reducti on in tumor size was documented in the liver. The primary tumor was no long er detectable by barium enema. The toxicity included three episodes of grad e 4 neutropenic fever, and two episodes of severe diarrhea and vomiting wit h dehydration. A cumulative grade 2 neurosensory toxicity was observed afte r six cycles. Following surgery of the primary tumor, because of the major hepatic tumor response and of the absence of extra-hepatic metastases, the patient might be registered for a liver transplantation program. This first report of combining the three active agents in CRC every 2 weeks led to a high dose intensity of each agent and was associated with a dramatic tumor response of a very advanced disease in a patient with already altered perfo rmance status. The antitumor activity in this patient suggests that a three -drug intensified regimen might be feasible and active. A prospective study appears warranted to further examine the efficacy and toxicity of this the rapeutic approach, and to determine whether it may increase the fraction of advanced CRC patients becoming resectable. This aggressive chemotherapy pr ogram may contribute to a re-examination of the usefulness of liver transpl antation in patients with metastatic CRC confined to the liver. [(C) 2000 L ippincott Williams & Wilkins.].