Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma.

PURPOSE: To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-alpha) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC. PATIENTS AND METHODS: Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-alpha (3 x 10(6) U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation. RESULTS: At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-alpha was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities. CONCLUSION: Results of this phase III trial do not support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.

A case-control study of dietary phytoestrogens and testicular cancer risk.

A few dietary studies have found elevated testicular cancer risks for higher red meat, fat, and milk intakes and lower intakes of fruits, vegetables, and fiber. Because hormonal modulation by dietary intake of plant estrogens could affect risk of testicular cancer, we chose to explore the possible relationship between dietary phytoestrogens and testicular cancer. We conducted a hospital-based case-control study of 159 testicular cancer cases diagnosed between 1990 and 1996 and 136 adult friend-matched controls at the University of Texas M. D. Anderson Cancer Center. Amounts of phytoestrogenic compounds in foods were added to the National Cancer Institute's DietSys program and then grouped into prelignans, lignans, flavonoids, isoflavonoids, phytosterols, and coumestrol for statistical analysis, expressed per 1,000 kcal. The results of multivariate logistic regression analysis showed, after adjustment for age, education, income, ethnicity, cryptorchidism, body mass index, baldness unrelated to therapy, severe acne in adolescence, early puberty, daily fiber and fat intake, and total daily calories, no discernable monotonic increased or decreased risk estimates across quartiles of phytoestrogen intake. A U-shaped pattern was observed for lignans and coumestrol. Further evaluation of this pattern by cubic spline parameterization did fit the data, but the data were also consistent with no effect. This hypothesis-generating study does not support the premise that dietary phytoestrogens increase or decrease testicular cancer risk in young men.