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Stage IV non-small cell lung cancer is a fatal disease, with a median survival of 14 months. Systemic chemotherapy is the most common approach. However the impact in overall survival and quality of life still a controversy. OBJECTIVES: To determine differences in overall survival and quality of life among patients with stage IV non-small cell lung cancer non-metastatic to the brain treated with best supportive care versus systemic chemotherapy. PATIENTS: From February 1990 through December 1995, 78 eligible patients were admitted with the diagnosis of stage IV non-small cell lung cancer . Patients were divided in 2 groups: Group A (n=31 -- treated with best supportive care ), and Group B (n=47 -- treated with systemic chemotherapy). RESULTS: The median survival time was 23 weeks (range 5 -- 153 weeks) in Group A and 55 weeks (range 7.4 -- 213 weeks) in Group B (p=0.0018). In both groups, the incidence of admission for IV antibiotics and need of blood transfusions were similar. Patients receiving systemic chemotherapy were also stratified into those receiving mytomycin, vinblastin, and cisplatinum, n=25 and those receiving other combination regimens (platinum derivatives associated with other drugs, n=22). Patients receiving mytomycin, vinblastin, and cisplatinum, n=25 had a higher incidence of febrile neutropenia and had their cycles delayed for longer periods of time than the other group. These patients also had a shorter median survival time (51 versus 66 weeks, p=0.005). CONCLUSION: In patients with stage IV non-small cell lung cancer, non-metastatic to the brain, chemotherapy significantly increases survival compared with best supportive care.

Background. Cancer of the male breast (MBC) is rare, accounting for less than 1% of cancer in males and representing less than 1% of all breast cancers. Reports of abnormalities in the expression of the tumor suppressor gene p53 in MBC have been few. Methods. To assess the expression and mutations of the p53 gene, 35 patients with 36 MBC (one patient with bilateral breast carcinoma) were examined using immunohistochemical methods, polymerase chain reaction (PCR)-single strand conformation polymorphism and DNA sequencing. Results. Thirty-one of the 36 carcinomas were studied by immunohistochemistry and by the PCR-based approach. Five patients were studied by immunohistochemistry only. Twelve patients (41.4%) of the 29 studied by molecular analysis presented an altered pattern in the single strand conformation polymorphism gel and point mutations were confirmed in all by direct DNA sequencing. Thirty-six tumors were studied by immunohistochemistry and 2 (5.5%) patients showed overexpression of the p53 protein. There were no statistically significant differences in p53 status with respect to : age, stage, estrogen receptors, progesterone receptors, tumor type. Patients with normal p53 showed a predisposition, although not statistically significant, for a longer disease free survival (5.6 years versus 4.2 years) and overall survival (5.9 years versus 4.8 years) than did patients with genetically altered p53. Conclusions. The incidence of male patients detected with p53 mutations (41.4%) in this series is concordant with the incidence of p53 mutations in female breast cancer, supporting the idea that cancer of the male breast is similar to the female counterpart. Cancer 1995 ;75 : 2233-8.

Chemotherapy with oxazaphosphorines, such as ifosfamide, is often limited by unacceptable urotoxicity. Without uroprotection hemorrhagic cystitis becomes dose-limiting. Mesna, a thiol compound, is a drug able to bind the toxic metabolites, forming nontoxic compounds in the urine. A total of 122 patients were enrolled in this study and 228 chemotherapy cycles with an ifosfamide-containing regimen were performed (225 evaluable). Mesna was given at the same total dose as the ifosfamide in all arms. On arm A, mesna was given i. v. in equal doses 15 min before and 4 h and 8 h following the ifosfamide dose. On arm B, mesna was given in three equivalent doses 15 min before (i.v.) and 4 h (i.v.) and 8 h (p.o., double dose) following ifosfamide. On arm C, mesna was given i.v. in two equal doses given 15 min before and 4 h following. The incidence of urotoxicity was very low (lower than 15%) in the three arms, 0% in A, 1.36% in B and 2.70% in C. All three arms were equally efficient. Schedule C was considered superior to the others, since it was equally effective, simpler and more convenient.

Background. Although an uncommon disease, male breast cancer (MBC) will be responsible for 300 deaths in 1993 in the United States. Because of the high rate of estrogen receptor positivity in males, adjuvant hormonal therapy with tamoxifen in the adjuvant setting has been used widely. Little is known about the side effects of this estrogen receptor blocker in males. Methods. The authors evaluated the side effects of adjuvant tamoxifen treatment in 24 patients (19 of whom were estrogen receptor positive) treated at the authors' institution between 1990 and 1993. Results. Fifteen (62.5%) patients reported at least one side effect. The most common side effect was a decrease in libido, which occurred in 7 (29.2%) patients; followed by weight gain, which occurred in 6 (25%) patients; hot flashes, which occurred in (5 20.8%); mood alterations, which occurred in 5 (20.8%); depression, which occurred in 4 (16.6%); insomnia, which occurred in 3 (12.5%); and deep venous thrombosis, which occurred in 1 (4.2%). Five (20.8%) patients terminated treatment with tamoxifen in less than 1 year because of these side effects. Two of these patients had decreased libido, two had hot flashes, and one suffered deep venous thrombosis. Conclusions. In contrast to female breast cancer patients, who have a 4% attrition rate to adjuvant tamoxifen treatment, MBC patients have a 20.8% attrition rate related to side effects of tamoxifen treatment.

Multiple factors, both environmental and genetic, are thought to play roles in breast carcinogenesis. The recently cloned multiple tumor suppressor gene (MTS1), the product of which interacts with CDK4 to regulate cell growth, has been found to be mutated with high frequency in a variety of cell lines as well as primary tumors of different histologic types. Using PCR-SSCP, we analyzed exons one (126 bp) and two (307 bp) of the MTS1 gene to determine the incidence of mutation in a population of 50 primary breast adenocarcinomas and corresponding normal tissue. Analysis of five breast tumor cell lines was also performed. We found no mutations in the MTS1 gene in the primary breast tumor samples. One cell line was found to have a homozygous deletion of the gene. Our results suggest that the MTS1 gene is not mutated with increased frequency in primary breast tumors, and thus may not play a major role in breast carcinogenesis.