Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. A randomised trial of octreotide vs best supportive care only in advanced gastrointestinal cancer patients refractory to chemotherapy. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.
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. Octreotide, a somatostatin analogue, has been shown to inhibit the growth of gastrointestinal cancers in vitro and in vivo. To assess the anti-tumour effect of octreotide, we performed a randomised trial comparing octreotide with best supportive care in advanced gastrointestinal cancer patients refractory to chemotherapy. A total of 107 patients with advanced gastrointestinal cancer refractory to chemotherapy were randomised to receive octreotide at the dose of 200 micrograms three times a day for 5 days a week, or the best supportive care only. The primary outcome variable was the survival duration. Response rate was an outcome variable of secondary importance. Fifty-five patients (15 stomach, 16 pancreas, 24 colon-rectum) received octreotide, while 52 (14 stomach, 16 pancreas, 22 colon-rectum) received the best supportive care. Patients treated with octreotide had a significant advantage in duration of survival with a median survival time of 20 weeks vs 11 in the control group (P < 0.0001). This advantage was present also considering the survival data for each tumour group. Twenty-five patients (45%) given octreotide showed stable disease vs only eight (15%) in the control group (P < 0.001). In conclusion, octreotide therapy seems to confer a survival benefit in advanced gastrointestinal cancer patients refractory to chemotherapy. Additional studies will be needed to confirm these results and to clarify other questions about dose and schedule of octreotide. 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.
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.