A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.

Summary The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin-or carboplatinbased therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than nonplatinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.Keywords: meta-analysis; systematic review; randomized controlled trials; advanced ovarian cancer; chemotherapy Health care professionals and patients alike are becoming increasingly aware of the need to make medical decisions on the basis of up-to-date, objective and unbiased research (Chalmers and Haynes, 1994). The most reliable information results from randomized controlled trials (RCTs). Unfortunately, most RCTs, including those conducted in ovarian cancer, have been too small to demonstrate moderate treatment benefits with reliability, and many results have been inconclusive or contradictory. The Advanced Ovarian Cancer Trialists Group (AOCTG) recognized that the best means of synthesizing such randomized evidence is by systematic meta-analysis. In 1988, five meta-analyses of chemotherapy in advanced ovarian cancer using updated individual patient data were initiated. The first results were published in 1991 (AOCTG, 1991). The AOCTG recognized the importance of updating these results especially for the comparison of carboplatin and cisplatin, in which the data were relatively immature. The comparison of platinum analogues was considered of such clinical importance that further new investigations were initiated to identify whether any particular type of women or tumour would benefit more from either cisplatin-or carboplatin-based chemotherapy. PATIENTS AND METHODSTrials were eligible for inclusion provided they examined first-line chemotherapy for advanced ovarian cancer, were properly randomized and made one of the treatment comparisons described below. Trials were identified by bibliographic searches using MEDLINE and CancerLit, by hand searching relevant meeting proceedings and by consulting trial registers (AOCTG, 1991). Both published and unpublished trials were included and updated data were sought for all randomized patients. All data were checked thoroughly and the final database entries for each trial were verified by the responsible trialist or data centre.All analyses were based on intention to treat. Survival analyses were stratified by trial, and t...

BACKGROUND Resection of pancreatic carcinoma is resource‐intensive with a limited impact on survival. Chemotherapy and/or radiotherapy (RT) have been shown to be effective palliation. To examine whether preoperative chemoradiotherapy as the initial treatment improves survival for patients with a regional pancreatic adenocarcinoma with a minimal chance of being resected successfully, an outcomes trial was conducted. METHODS Patients with radiologically regional tumors were staged by laparotomy and/or computed tomography followed by endoscopic ultrasonography, angiography, and/or laparoscopy. Those with locally invasive, unresectable, regional pancreatic adenocarcinoma initially were treated with simultaneous split‐course RT plus 5‐fluorouracil, streptozotocin, and cisplatin (RT‐FSP) followed by selective surgery (Group 1). Patients determined to have a resectable tumor initially underwent resection without preoperative chemoradiotherapy, with or without postoperative chemoradiotherapy (Group 2). RESULTS Over 8 years 159 patients presenting with nonmetastatic pancreatic adenocarcinoma were administered RT‐FSP or underwent surgery for resection. Group 1, comprised of 68 patients initially treated with RT‐FSP, had a 0% mortality rate within 30 days of entry. In 20 of 30 patients undergoing surgery after RT‐FSP, tumors were downstaged and resected. Group 2, comprised of 91 patients who initially underwent successful resection, had a 5% mortality rate within 30 days of entry. Postoperatively, 63 of these patients received chemotherapy with or without RT. The median survival for Group 1 was 23.6 months compared with 14.0 months for Group 2 (P = 0.006) despite more advanced disease cases in Group 1. Survival favored RT‐FSP regardless of whether lymph nodes were malignant. The dominant prognostic factor of earlier stage pancreatic carcinoma having an expected survival advantage was reversed by the initial nonoperative treatment. CONCLUSIONS Based on a reversal of the expected trend that patients with earlier stage resectable carcinoma (T1,2, N0,1, M0) who undergo removal of their tumors survive longer than patients with more advanced regional disease (T3, N0,1, M0), survival was found to improve significantly for patients reliably staged as having locally invasive, unresectable, nonmetastatic pancreatic adenocarcinoma when initially treated with RT‐FSP. Cancer 2000;89:314–27. © 2000 American Cancer Society.

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The expression of sialosyl-Tn (STn) antigen was evaluated by immunohistochemistry in primary gastric cancers. Twenty-one of 31 (68%) gastric cancers expressed STn, regardless of tumour location, stage or histological type. Eighty-one per cent of patients with STn-positive tumours died of their disease or had recurrent cancer, compared with 20% of patients with STn-negative tumours (P < 0.002). STn may be a useful prognostic marker in patients with gastric cancer. Images Figure 1

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Background. Single agents have only modest activity as treatment for metastatic pancreatic cancer with response rates of less than 10% and median survivals of less than 6 months. Evaluations of single-agent gemcitabine and rubitecan as second-line treatment for relapsed pancreatic cancer have reported good patient tolerability and median survivals of 3.85 months and 4.7 months, respectively. Regimens incorporating two drugs have demonstrated encouraging activity and clinical impact compared with single-agent therapy. G-FLIP is a regimen designed to incorporate four active single agents into a tolerable and active combination. This analysis is a retrospective evaluation of the efficacy and safety of the G-FLIP regimen as second-line chemotherapy in a series of consecutively treated patients with metastatic pancreatic cancer.Methods. G-FLIP was administered over 48 hours and repeated every 2 weeks. Day 1 treatment consisted of sequentially administered gemcitabine 500 mg/m

This radomized double-blind study was designed to compare the therapeutic effectiveness of the oral and i.v. routes for 5-FU administered in intensive courses to 100 patients with metastatic adenocarcinoma of the large bowel, treated to equivalent levels of toxicity. An oral dose of 20 mg/kg day times 5 was found to produce comparable G.I., mucocutaneous, and hematologic side effects to a dose of 13.5 mg/kg day times 5 by rapid i.v. injection. Courses were repeated at 5 weeks. Nine of 47, or 19.1%, treated by the oral route have shown objective response, compared to 14 of 53, or 26%, treated by the i.v. route. If malignant hepatomegaly is considered alone, the response rates are 8 of 23, or 34.8%, by the oral route, and 7 of 22, or 31.8%, by the i.v. route. The mean duration of response for the oral group, 11.1 weeks, was shorter than for the i.v. route, 20 weeks, a statistically significant (p less than 0.02) difference. Serial serum 5-FU levels after two doses of 5-FU were determined by microbiological assay in 19 patients. For i.v. administration the curves were comparable among different patients as well as in the same patient. There was striking variability, however, for oral administration.