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Abstract: The authors evaluated the impact of a chronotherapy with 5-FU, folinic acid and carboplatine (chronomodulated infusions by ambulatory pumps; 5/21 days) for the management of oesophagus (52 cases) and gastric (56 cases) cancer patients. The overall tolerance of treatment was gauged excellent (grade 3–4; % patients: mucitis: 11–23%; leucopenia 6–19%; thrombopenia 18–50%; almost no digestive disturbances nor alopecia). Also tumor outcome was considered interesting with major responses rate in 61% (gastric) to 79% (oesophagus) of patients. The median survival of oesophageal cancer was limited to 9.2 months; the one of disseminated gastric cancer was 12.7 months but 72% of curatively resected patients were alive at 5+years. [Copyright &y& Elsevier]

Abstract: Thirty-seven patients operated from a Dukes B2-C colon cancer were randomised to receive as adjuvant infusional chemotherapy, nine 5 FU and folinic acid courses with or without carboplatin, as standard (de Gramont ; 2 days every 2 weeks) or chronomodulated administration (4 days every 2 weeks). The overall tolerance was judged excellent with less than 7% courses with dose-adaptations. The two carboplatin arms presented an enhanced haematological toxicity, while some more cutaneous toxicity was observed in the chronomodulated arm with the three drugs. [Copyright &y& Elsevier]

Abstract: Seventeen colorectal cancer patients received as first (12 cases) or second line (5 cases) treatment a combined chronotherapy with CPT 11 (infused at day 1 from 2 to 8 am; peak at 5 am), given with 5 FU (700 mg/m2 per day ; days 2–5) and folinic acid (300 mg/m2 per day, days 2–5) both infused from 10 pm to 10 am with a peak at 4 am, and carboplatin (40 mg/m3/day – days 2–5 ; infused from 10 am to 10 pm – peak at 4 pm). The doses of CPT 11 could be easily increased from 120 up to 180 mg/m2 in successive cohorts of four patients through acceptable toxicity. Thus, five patients have already been treated in the phase II part of the trial. An interesting tumoral outcome has been observed: 88% major responses with no progression; median time to progression: nine months and median survival: 19.7 months. [Copyright &y& Elsevier]

Abstract: Seventy-two patients suffering from a metastatic colorectal cancer received, as first line treatment, a combination chronotherapy with 5-FU and folinic acid (infused from 10 pm to 10 am with a peak at 4 am, respectively at doses of 700 and 300 mg/m2 per day) and carboplatin (infused at the dose of 40 mg/m2 per day from 10 am to 10 pm with a peak at 4 pm). The courses of four days were repeated every two weeks. A major tumoral response was observed in 60% cases (68% in those not previously treated with adjuvant chemotherapy). The median times to progression and overall survival established at 11 and 27 months. The clinical (grades 3–4 in maximum 5% cases) and hematological (grades 3–4 in maximum 10–29% cases) toxicities were quite limited. Our observations suggest the interest to incorporate carboplatin in the combined infusional treatment of colorectal cancer. [Copyright &y& Elsevier]

Abstract: Thirty-six metastatic colorectal cancer patients received every 2 weeks, as first- (17) or second-line (19) treatment a combined chronotherapy with CPT-11 (infused at day 1 from 2 to 8 a.m.; peak at 5 a.m.), given with 5FU (700 mg/m2 per day; days 2–5) and folinic acid (300mg/m2 per day; days 2–5) both infused from 10 p.m. to 10 a.m. with a peak at 4 a.m., and carboplatin (40mg/m2 per day; days 2–5; infused from 10 a.m. to 10 p.m.; peak at 4 p.m.). The doses of CPT11 could be easily pushed from 120 to 180mg/m2 in successive cohorts in the phase I part of the study (11 cases). Twenty-five patients were then treated in the phase II of the trial. The overall toxicity was mild leading to dose-reductions in only 11–13% courses. The tumoral activity was interesting with 81% responses and 94% tumour control. Also prolonged survivals were recorded with 8.8months of progression free and 15.6months overall survivals. More prolonged survivals were observed in chemotherapy naive patients. Seven patients (19%) could be reoperated from their residual disease. [Copyright &y& Elsevier]