Mucinous histology predicts for poor response rate and overall survival of patients with colorectal cancer and treated with first-line oxaliplatin- and/or irinotecan-based chemotherapy.

The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5-29.2%) and 49% (95% CI, 42.2-55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27-3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05-2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites > or =2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.

Feasibility of a cell kinetic-based adjuvant chemotherapy trial in axillary node-negative breast cancer.

AIMS AND BACKGROUND: Accumulated information on biologic prognostic indicators and predictors of response to different types of treatment in patients with different tumor characteristics has made it possible to design clinical protocols on biologic bases. Among cell proliferation indices, the thymidine labelling index (TLI) has proved to be an independent and consistent prognostic indicator over time. Moreover, experimental and retrospective analyses of clinical studies have revealed a direct relation between TLI and response to chemotherapy. On the basis of the results, a prospective clinical protocol on axillary node-negative breast cancer was activated in Italy in 1989. METHODS: Patients with low TLI tumors were treated with local-regional therapy alone, whereas patients with high TLI tumors were randomized to receive local-regional therapy followed or not by adjuvant chemotherapy consisting of 6 cycles of CMF. RESULTS AND CONCLUSIONS: The present paper reports on the feasibility of a prospective clinical protocol based on a subgroup of patients with specific pathologic (node negative) and biologic (rapidly proliferating) breast cancers. However, patient eligibility was only 11%.

Oral cooling (cryotherapy), an effective treatment for the prevention of 5-fluorouracil-induced stomatitis.

Recently, a randomised study demonstrated the utility of oral cooling (cryotherapy) in the prevention of 5-fluorouracil (5FU)-induced stomatitis. In order to verify these results a confirmatory study, using identical treatment regimen, was initiated. 84 patients treated with a 5-FU-containing regimen were randomised to a control arm or to receive oral cryotherapy. End point evaluation was obtained by a global assessment of the physician's judgement and patients' description of mucositis severity graded 0-4. Mucositis was significantly reduced by cryotherapy considering both the first cycle of therapy (the mean toxicity score for cryotherapy was 0.59 and it was 1.1 for the control group, P < or = 0.05) and all the chemotherapeutic courses (the mean toxicity score for cryotherapy was 0.36 when it was 0.69 for the control group, P < or = 0.05). In conclusion, the present study confirms that cryotherapy can decrease 5FU-induced stomatitis and should be recommended for patients receiving bolus 5FU-containing regimens.

Control of chemotherapy-induced diarrhea with octreotide. A randomized trial with placebo in patients receiving cisplatin.

Cisplatin-related diarrhea is a relatively common complication in the clinical management of cancer patients and until now no treatment for this condition has been identified. Octreotide has been reported effective in the treatment of 5-fluorouracil-related diarrhea. To assess the safety and efficacy of octreotide in controlling diarrhea caused by cisplatin, 43 patients who had already had diarrhea during the 24-hour period following a previous cisplating administration were randomized to receive either octreotide or placebo during the next cisplatin course. The patients given octreotide experienced less diarrhea (5 vs. 75%, p = 0.01). There were no side effects. We conclude that octreotide is more effective than placebo in controlling diarrhea following cisplatin chemotherapy.

Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial.

PURPOSE: Diarrhea is a prominent feature of fluorouracil (5FU) gastrointestinal toxicity, especially when 5FU is combined with leucovorin (LV) or interferon (IFN). No treatment for this condition has been well defined, although drugs, such as diphenoxylate or loperamide, generally are used. The efficacy of octreotide in the treatment of 5FU-induced diarrhea recently has been reported. We performed a randomized trial that compared octreotide with loperamide, the drug most commonly used for therapy for this disorder. PATIENTS AND METHODS: Forty-one patients with grade 2 (four to six stools per day) or grade 3 (seven to nine stools per day; National Cancer Institute toxicity criteria) diarrhea after chemotherapy with a 5FU-containing regimen for colorectal cancer in 28 cases, gastric cancer in six cases, pancreatic cancer in five cases, and breast cancer in two cases, were entered onto the study. Twenty-one patients received octreotide at a dosage of 0.1 mg subcutaneously twice per day for 3 days, and 20 patients received loperamide 4 mg orally initially and then 2 mg every 6 hours for 3 days. The two arms were comparable for age, sex, and primary tumor. Patients were evaluated for response each treatment day; all patients were assessable. RESULTS: Diarrhea resolved in 19 patients in the octreotide arm (one within the first day; four within the second day; and 14 within the third day) versus only three (all after the third day of therapy) in the loperamide arm (P < .005). Median frequency of stools in the 3 days of therapy was four, three, and zero in the octreotide arm and five, five, and five in the loperamide arm. No side effects were observed in both arms. Ten patients on the loperamide arm and only one on the octreotide arm required hospitalization for parenteral replenishment of fluids and electrolytes. CONCLUSION: Octreotide seems to be more effective than loperamide in control of diarrhea and elimination of the need for replenishment of fluids and electrolytes.

5-Fluorouracil, leucovorin and interferon alpha 2b in advanced pancreatic cancer: a pilot study.

BACKGROUND: On the basis of data suggesting the possibility of maximizing the efficacy of 5-FU by LV and IFN, a pilot clinical trial was initiated in advanced pancreatic cancer. PATIENTS AND METHODS: Twenty-four patients received weekly 5-FU 600 mg/m2 bolus 1 hour after the initiation of a 2-hour infusion of 500 mg/m2 of leucovorin. Three MU of interferon alpha 2b was administered subcutaneously three times a week. RESULTS: Two of 22 evaluable patients obtained partial responses (8%, confidence interval 3%-33%). Toxicity was severe. Diarrhea and stomatitis were the most common side effects, occurring in 50% and 25% of patients, respectively. CONCLUSION: Because of the presence of severe toxicity we suggest that further clinical trials in pancreatic cancer be attempted only after a better definition in preclinical studies of interactions among 5-FU, leucovorin and interferon.

Cisplatin-associated anaemia treated with subcutaneous erythropoietin. A pilot study.

In 20 patients with cisplatin-associated anaemia (haemoglobin less than 90 gl-1), recombinant human erythropoietin was administered subcutaneously three times a week on an outpatient basis. The initial dose was 50 Units Kg-1 of body weight. If response was not achieved within 3 weeks, dose was increased to 75 Units Kg-1. Using the same criteria further escalation to 100 Units Kg-1 was performed. If there was no response erythropoietin was terminated. Fifteen patients obtained an increase in haemoglobin to above 100 gl-1 which was considered as a clinical response in this study, with a dose of 50 Units Kg-1; one patient needed an erythropoietin dose of 75 Units Kg-1 and one a dose of 100 Units Kg-1. Only three patients required haemotransfusions and were considered non responders. Haemoglobin increases occurred despite continuation of cisplatin chemotherapy. In conclusion subcutaneous low dose of erythropoietin seems to be effective and safe in the treatment of cisplatin-induced anaemia.

Double biochemical modulation of 5-fluorouracil by leucovorin and cyclic low dose interferon alpha 2b in advanced colorectal cancer patients.

Because of the different sites and mechanisms of biochemical interaction among 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN), we hypothesized that the concomitant use of IFN could increase the activity of the 5-FU/LV combination in colorectal cancer patients. Forty-five patients were included in the study and all were evaluable for response and toxicity. They were treated with 5-FU 370 mg/sqm i.v. d 2-6; LV 200 mg/sqm i.v. d 2-6; IFN alpha 2b 3 million U im d 1-7 every 21 days. Six patients achieved complete responses, 17 partial responses, 14 had stable disease and 8 progressed on therapy for an overall response rate of 51%. Median survival has not been reached. At a median follow-up of 14 months 33 of 45 patients remain alive. Nine patients experienced toxicity grade 3 (6 diarrhea and 3 stomatitis). Our results seem to suggest that IFN could increase 5-FU/LV activity and that this combination is well tolerated.

Control of chemotherapy-induced diarrhoea with octreotide in patients receiving 5-fluorouracil.

Chemotherapy treatment with combination of 5-fluorouracil and leucovorin or interferon alpha determined an incidence of severe diarrhoea of 10 and 20%, respectively. Up to date no treatment for this condition has been defined. 21 patients affected by advanced colorectal cancer and 6 patients affected by advanced pancreatic cancer received octreotide as treatment for severe diarrhoea following chemotherapy with 5-fluorouracil/leucovorin (Machover's regimen) or 5-fluorouracil/interferon (Wadler's regimen) combination. Octreotide was administered by subcutaneous injection of 50 micrograms twice daily on the first day and 100 micrograms twice daily on the second and third day. 26 patients had total cessation of diarrhoea: 4 patients within the first day, 6 within the second day and 16 within the third day. 1 patient had no change and after the last administration of octreotide he was treated with loperamide and intravenous hydration. Side effects have been mild. In summary octreotide seems to be an effective agent in the management of chemotherapy related diarrhoea.

Experience with intrapleural natural beta interferon in the treatment of malignant pleural effusions.

Malignant pleural effusion is a common complication of cancer. Intrapleural beta interferon has been recently tested, and responses were obtained in about 1/3 of the patients without considerable side effects. We treated 22 patients with recurrent symptomatic malignant pleural effusions with intrapleural beta interferon at increasing doses (5-15 million units) for a maximum of three courses and obtained only two responses. In our opinion, this schedule cannot be recommended for routine use.