A Pilot Evaluation of Alternating Preoperative Chemotherapy in the Management of Patiens with Locoregionally Advanced Breast Carcinoma

BACKGROUND: This prospective trial was conducted to evaluate the outcome of patients treated with preoperative and post operative chemotherapy, mastectomy, and irradiation for locoregionally advanced breast carcinoma. METHODS: Between June 1986 and September 1990, 71 patients received 2 cycles of doxorubicin that alternated with 2 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil prior to mastectomy; irradiation was administered when the tumor was not amenable to surgical resection. Additional chemotherapy and tamoxifen, in hormone receptor-positive tumors, was used after mastectomy. Post-operative irradiation was given on a selective basis for patients at high risk for locoregional disease recurrence. RESULTS: Although 5 patients (7%) had disease progression, clinical partial or complete tumor response to preoperative chemotherapy was noted in 46 patients (65%). Sixty-eight patients (96%) underwent mastectomy. With a median follow-up of 52 months, the relapse-free and overall survival rates at 5 years were 42% and 57% respectively. Locoregional tumor recurrence occurred in 14 patients (20%), and 28 patients (39%) developed metastatic disease. Menopausal status, clinical presentation (noninflammatory vs. inflammatory), and American Joint Committee on Cancer clinical stage were independent covariates associated with patient outcome. CONCLUSIONS: Preoperative alternating chemotherapy, with the selective use of irradiation, resulted in significant locoregional disease regression and the successful integration of mastectomy into the therapeutic strategy. Locoregional tumor control and relapse-free and overall survival estimates for the approach described herein compared favorably with other comtemporary reports for this condition

Alleviation of Gastrointestinal Mucosal Toxicity Related to Chemotherapy and Radiation Therapy: The NCCTG Experience.

Purpose. Cancer patients undergoing chemotherapy and radiation therapy may experience substantial mucosal toxicity. The North Central Cancer Treatment Group (NCCTG) has developed a series of Phase III clinical trials to study agents to alleviate mucosal injury. This manuscript will review this experience. Results. An NCCTG trial demonstrated that oral cryotherapy for 30 minutes is able to decrease 5-FU stomatitis by approximately 50%. This result was replicated in an independent trial. Other NCCTG trials evaluating means of reducing 5-FU-induced stomatitis have demonstrated lack of efficacy for allopurinol mouthwashes, chamomile mouthwashes, a sucralfate slurry, and oral glutamine. Trials evaluating means of alleviating radiation-induced oral mucositis have demonstrated that a chlorhexidine mouthwash is detrimental while oral non-absorbable antibiotic lozenges may provide some marginal benefit, but not enough to recommend it for standard clinical practice. A single trial evaluating radiation-induced esophagitis failed to demonstrate any benefit for a sucralfate slurry. Three trials have been developed to evaluate means for alleviating radiation-induced proctitis. The first trial demonstrated that olsalazine was detrimental in this situation. A second trial, evaluating sucralfate, closed in June 1997. A third trial, designed to evaluate glutamine, is being readied to initiate patient entry. Conclusions. The NCCTG, through a program of randomized, placebo-controlled, clinical trials, has been able to evaluate whether purported treatment options are beneficial for the alleviation of mucosal injury from cancer treatment

Sex Differences in Fluorouracil-Induced Stomatitis.

PURPOSE: A meta-analysis of six North Central Cancer Treatment Group (NCCTG) trials involving patients receiving their first ever fluorouracil (5-FU)-based chemotherapy was undertaken to explore the association of sex with reports of the incidence and severity of stomatitis. PATIENTS AND METHODS: Data were obtained on a total of 731 patients (402 men and 329 women). Comparisons of incidence and severity rates and average stomatitis across sex were performed using standard binomial testing and t tests, respectively. Logistic regression analysis and a weighted analysis using data summarized to study level served as evidence of cross-validation. RESULTS: Women reported stomatitis both more often and with greater severity than did men. The incidence of any stomatitis for women was 63% versus 52% for men (P =.002). The incidence of severe or very severe stomatitis for men and women was 22% and 12%, respectively (P =. 0006). On average, women reported stomatitis of roughly 0.4 points higher than men on a 0 to 4 ordinal scale (P/= 1, (70% v 59%, respectively; P CONCLUSION: More women than men reported 5-FU-induced stomatitis. The precise mechanism resulting in different degrees of stomatitis across sex is not evident

An Eicosapentaenoic Acid Supplement Versus Megestrol Acetate Versus Both for Patients with Cancer-Associated Wasting: A North Central Cancer Treatment Group and National Cancer Institute of Canada Collaborative Effort.

PURPOSE: Studies suggest eicosapentaenoic acid (EPA), an omega-3 fatty acid, augments weight, appetite, and survival in cancer-associated wasting. This study determined whether an EPA supplement-administered alone or with megestrol acetate (MA)-was more effective than MA. PATIENTS AND METHODS: Four hundred twenty-one assessable patients with cancer-associated wasting were randomly assigned to an EPA supplement 1.09 g administered bid plus placebo; MA liquid suspension 600 mg/d plus an isocaloric, isonitrogenous supplement administered twice a day; or both. Eligible patients reported a 5-lb, 2-month weight loss and/or intake of less than 20 calories/kg/d. RESULTS: A smaller percentage taking the EPA supplement gained \u3eor= 10% of baseline weight compared with those taking MA: 6% v 18%, respectively (P =.004). Combination therapy resulted in weight gain of \u3eor= 10% in 11% of patients (P =.17 across all arms). The percentage of patients with appetite improvement (North Central Cancer Treatment Group Questionnaire) was not statistically different: 63%, 69%, and 66%, in EPA-, MA-, and combination-treated arms, respectively (P =.69). In contrast, 4-week Functional Assessment of Anorexia/Cachexia Therapy scores suggested MA-containing arms experienced superior appetite stimulation compared with the EPA arm, with scores of 40, 55, and 55 in EPA-, MA-, and combination-treated arms, respectively (P =.004). Survival was not significantly different among arms. Global quality of life was not significantly different among groups. With the exception of increased impotence in MA-treated patients, toxicity was comparable. CONCLUSION: This EPA supplement, either alone or in combination with MA, does not improve weight or appetite better than MA alone

Women Experience Greater Toxicity with Fluorouracil-Based Chemotherapy for Colorectal Cancer.

PURPOSE: The toxicity profile of fluorouracil (5-FU)-based chemotherapy given on 5 consecutive days at doses of 370 to 450 mg/m(2) has been well documented. A meta-analysis of six North Central Cancer Treatment Group (NCCTG) cancer control trials involving 786 patients indicated that women treated with this type of regimen experienced more severe stomatitis and leukopenia than men. After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken. METHODS: Data for 1,093 women and 1,355 men from 12 different treatment arms were included. The primary end points were the incidence of stomatitis, leukopenia, alopecia, diarrhea, nausea, and vomiting, recorded with standard National Cancer Institute common toxicity criteria. Fisher\u27s exact test was used to compare incidence and severity across sexes, supplemented by Forrest meta-analysis plots and logistic regression. RESULTS: The incidence of four out of six toxicities studied was significantly greater for women than men; the exceptions were severe nausea and vomiting. Overall, almost half of the women compared with a third of the men experienced severe toxicity (P CONCLUSION: This study confirms an earlier finding that women receiving 5-FU-based chemotherapy in a 5-day bolus schedule experience toxicity more frequently and with more severity than men. These data raise the question of whether the recommended initial dose of 5-FU-based chemotherapy for women should be lower than that for men