Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group.
To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care.
                Randomised study.
                Gastrointestinal oncology departments.
                40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic.
                Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle.
                Length of survival and quality of life score with an optimised functional living index-cancer scale.
                Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm.
                In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment. The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients.
                Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument.
                More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03).
                The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited. In a prospective multicenter trial, 279 patients with metastatic colorectal cancer who had failed 5-fluorouracil therapy were randomized 2:1 to receive either best supportive care (BSC) plus treatment with the topoisomerase I inhibitor, irinotecan (CPT-11; Rhône-Poulenc Rorer, Antony, France), at a dose of 350 mg/m2 every 3 weeks or BSC alone. Overall survival, the primary end point of the study, was significantly improved in patients receiving the irinotecan treatment. Only 14% of patients receiving BSC alone were alive at 1 year compared with 36% in the irinotecan group. After adjustment for prognostic factors such as performance status, the difference in survival favoring irinotecan remained highly significant (P = .001). The benefit of irinotecan was also observed through significantly longer survival without performance status deterioration, longer survival without more than 5% weight loss, and longer duration of pain-free survival. Appreciable deterioration in global quality of life (50% reduction from baseline) occurred significantly later in the irinotecan-treated patients than in the controls. Additionally, quality of life analyses of all symptoms, except diarrhea, mean scores were significantly in favor of patients assigned to irinotecan treatment than those assigned to BSC. This is the first time that the benefit of second-line chemotherapy has been demonstrated by a randomized controlled trial in advanced colorectal cancer.
Overall the results show that for most of the studies included in this review, certain forms of chemotherapy plus supportive care improve both survival and quality of life in patients with gastrointestinal cancer (gastric and colorectal cancers) compared to receiving supportive care alone. Trials involving BSC/SC in patients with advanced gastrointestinal cancer require careful evaluation. Oncologists and researchers alike should strive for improvements in trial design and reporting. Future trials should focus on clearer definitions of supportive care. The EORTC definition of supportive care can be used as a guide. BSC/SC trials should use standardised validated outcome measures for symptom control, quality of life, toxicity and other useful palliative measures.