Long-term follow-up of a Phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292).

PURPOSE: Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. METHODS AND MATERIALS: Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m(2)/day on Days 1 to 4 and cisplatin 75 mg/m(2) on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. RESULTS: Complete response was seen in 78% (90% CI, 63-89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. CONCLUSIONS: Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.

A long-term analysis of 1018 patients with melanoma by classic Cox regression and tree-structured survival analysis at a major referral center: Implications on the future of cancer staging.

BACKGROUND: Traditional statistical analysis of 2 surgeons' experiences with resectable malignant melanoma during a 30-year period (November 1970-July 2000) was compared with new tree-structured recursive partitioning regression analysis. METHODS: A total of 1018 consecutive patients were registered and 983 patients were evaluable. Disease-free survival (DFS) and melanoma survival (MS) were calculated by Kaplan-Meier method for stage, thickness, ulceration, site, lymph node involvement, age, sex, and type; and compared with log-rank tests. Cox proportional hazards model was used for multivariate analysis. Multivariate predictors were used to analyze DFS and MS with a classification and regression tree model that partitioned patients into progressively more homogenous prognostic groups with significantly different Kaplan-Meier curves. RESULTS: Multivariate correlations were with thickness (millimeters), ulceration, age (per year), type, and sex in predicting DFS (relative risk = 1.18, 2.10, 1.05, 1.71, and 1.71, respectively). Thickness, ulceration, age, and type remained significant predictors of MS (relative risk = 1.14, 3.02, 1.02, and 2.30, respectively). Classification and regression tree analysis showed thickness, age, ulceration, and sex affected DFS. Only thickness and ulceration were significant in predicting MS. CONCLUSION: The Cox model is an important tool for analysis of clinical data but has flaws. New statistical technology to predict outcome should be considered. Classification and regression tree analysis of larger published series may reveal new predictors useful for staging, prognosis, and guiding clinical decisions.