Sexual difficulties, concerns, and satisfaction in homosexual men: an empirical study with implications for HIV prevention.

Minimal research has investigated the prevalence of sexual disorders in homosexual men. We examined sexual performance concerns, problems, and satisfaction in a convenience sample of 197 homosexual men who attended a health seminar. Sexual dysfunction and sexual concerns were found to be common problems. Almost all men reported some sexual difficulty over their lifetime, and more than half reported a current sexual difficulty. A further 25% of the sampled men identified other sexual concerns as well. Despite these figures, most participants-whether single, dating, or in a relationship-reported average to above-average sexual satisfaction. Correlates of sexual satisfaction included more liberal attitudes toward human sexuality, greater comfort with men's sexual attractions to other men, lower levels of internalized homophobia, and greater satisfaction with one's relationship status. Painful receptive anal intercourse appeared to be a common, yet previously underacknowledged, difficulty. Almost half of the respondents described HIV/AIDS as having a negative impact on their sexual functioning, with most reporting an increase in fear of sex as the major negative outcome.

Gene therapy for the treatment of malignant brain tumors with in vivo tumor transduction with the herpes simplex thymidine kinase gene/ganciclovir system.

Murine retroviral vectors can infect a wide variety of proliferating mammalian cell types (e.g. lymphocytes). Non-proliferating tissues (e.g. neurons) are not transduced by murine retroviral vectors. These findings suggest that this type of vector may be useful for the selective introduction of genes into growing tumors in the brain, since the tumor is essentially the only tissue that will integrate and express the vector genes.

Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer.

PURPOSE: To compare two commonly used schedules of fluorouracil (5FU) and leucovorin in the treatment of patients with advanced metastatic colorectal cancer. Each of these dosage administration schedules has been demonstrated to be superior to single-agent bolus 5FU in previous controlled trials. PATIENTS AND METHODS: Three hundred seventy-two ambulatory patients with metastatic colorectal cancer were stratified according to performance status, and presence and location of any measurable indicator lesion(s). They were then randomized to receive chemotherapy with one of the following regimens: (1) intensive-course 5FU plus low-dose leucovorin (5FU 425 mg/m2 plus leucovorin 20 mg/m2 intravenous [IV] push daily for 5 days with courses repeated at 4- to 5-week intervals); (2) weekly 5FU plus high-dose leucovorin (5FU 600 mg/m2 IV push plus leucovorin 500 mg/m2 as a 2-hour infusion weekly for 6 weeks with courses repeated every 8 weeks). RESULTS: Three hundred sixty-two of 372 patients randomized (97.3%) were eligible and included in the analysis. Three hundred forty-six patients (95.6%) have died. There were no significant differences in therapeutic efficacy between the two 5FU/leucovorin regimens tested with respect to the following parameters: objective tumor response (35% v 31%), survival (median, 9.3 v 10.7 months), and palliative effects (as assessed by relief of symptoms, improved performance status, and weight gain). There were significant (P < .05) differences in toxicity, with more leukopenia and stomatitis seen with the intensive-course regimen, and more diarrhea and requirement for hospitalization to manage toxicity with the weekly regimen. Financial cost was also higher with the weekly regimen. CONCLUSION: Intensive-course 5FU plus low-dose leucovorin appears to have a superior therapeutic index compared with weekly 5FU plus high-dose leucovorin using the dosage administration schedules applied in this study based on similar therapeutic effectiveness, but lower financial cost, and less need for hospitalization to manage chemotherapy toxicity.

A randomized prospective assessment of recombinant leukocyte A human interferon with or without aspirin in advanced renal adenocarcinoma.

We performed a prospective, controlled trial of recombinant leukocyte A interferon (IFN-alpha 2A) with or without aspirin (ASA) in 176 patients with assessable advanced renal cell cancer in light of a 34% response rate (10 of 29 patients) from the two-agent regimen in an earlier nonrandomized trial. This encouraging result was substantially higher than the 15% response rate typically achieved with IFN therapy alone. Eighty-seven patients received IFN-alpha 2A 20 x 10(6) U/m2 intramuscularly three times a week, and 89 received the same IFN therapy with ASA 600 mg orally four times each day. Each group was balanced as to relevant prognostic discriminants. Response rates were 8% for the group receiving ASA in addition to IFN, and 13% for the group receiving IFN alone (P = .30). The median times to progression were 1.9 months for the group receiving IFN with ASA and 2.7 months for the group receiving IFN alone (log-rank P = .36). The median survival durations were 8.8 months for the IFN and ASA group and 8.0 months for the IFN-only group (log-rank P = .60). These figures are also inferior to those typically reported from other studies. Our findings reemphasize the crucial role of randomized trials, admittedly cumbersome and time-consuming, to determine accurately the value of apparently promising therapies. Although some patients may derive benefit from IFN therapy, our findings raise disturbing questions regarding the potential IFN-alpha 2A according to the dose and schedule used in this trial to have any substantive impact on the ultimate outcome of disseminated renal cell cancer.

A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma.

Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5-FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma.

Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy.

An analysis of preoperative multimodality adjuvant therapy with 5-fluorouracil, mitomycin-C, and radiation therapy revealed that 38 of 45 patients (84 percent) treated were rendered free of cancer after chemotherapy/radiation therapy. No recurrence of tumor has been noted in those patients rendered free of disease by the preoperative treatment. Seven patients (15 percent) with residual macroscopic or microscopic cancer after preoperative therapy have had recurrence, all in distant sites. These seven patients have died from the disease. The prognosis for patients in this series depended on the success of the preoperative therapy in eradicating all tumor prior to surgery. Mitomycin-C and 5-fluorouracil are cytotoxic for local disease and for microscopic distant disease as well. Abdomino-perineal resection is unnecessary for patients whose primary tumor is eradicated by the preoperative therapy. The role of the relatively low dose of radiation therapy needs to be further defined.

Eradication and palliation of squamous cell carcinoma of the esophagus with chemotherapy, radiotherapy, and surgical therapy.

Between April, 1977, and March, 1981, 86 unselected patients with proved squamous cell carcinoma of the esophagus were treated with a combination of chemotherapy and radiotherapy followed by operation whenever feasible. The preoperative chemotherapeutic agents used initially were 5-fluorouracil, and mitomycin C. After December, 1979, cis-platinum was used instead of mitomycin C. Radiotherapy (3,000 rads) of the tumor was begun at the same time as the chemotherapy. An esophagectomy was performed on suitable candidates 3 to 4 weeks after the chemotherapy and radiotherapy were completed. The mucosal lesion disappeared in 69 of the 86 patients, and dysphagia was relieved at least temporarily in 57 of 62 patients. Recurrent dysphagia resulting from fibrosis at the tumor site caused a secondary stenosis in 11 patients. Excellent palliation was obtained in five patients with bronchoesophageal fistulas who had an initial substernal gastric bypass followed by chemotherapy and radiotherapy. Of the 48 patients who had an esophagectomy, 15 (31%) had no tumor in the resected specimen. Eleven of these 15 patients are still alive with no evidence of disease. All patients with a lesion less than 5.0 cm in length had complete regression of the tumor. We believe that this combination of chemotherapy, radiotherapy, and surgical therapy provides excellent palliation, increases resectability, and has a potential for cure.

Combined therapy for cancer of the anal canal.

Nineteen patients with squamous-cell cancer of the anal canal have been treated with combined chemotherapy and radiation therapy, followed by appropriate surgery. The authors are convinced that the combined therapy is effective enough to avoid abdominoperineal resection if disappearance of the lesion is proven by adequate examination and biopsy. Although they believe cancers 5 cm or less in maximum diameter are generally adequately managed in this manner, experience is still too limited to justify a recommendation to change currently accepted management.

Pharmacokinetics of 5-fluorouracil administered orally, by rapid intravenous and by slow infusion.

Pharmacokinetic studies of 5-fluorouracil (5-FUra) were performed on 18 patients divided into three groups: seven patients were given 5-FUra i.v. by rapid injection; five patients received the drug p.o.; and six patients were treated by continuous i.v. infusion for 96 hr. The results showed rapid i.v. injection to be manifested by high early levels of drug achieved both in plasma and bone marrow with a rapid fall afterwards. Administration of 5-FUra p.o. gave rise to erratic plasma values due to greater variability in absorption, whereas 96-hr i.v. infusions showed constant levels of the drug in plasma and significantly (50- to 1000-fold) less 5-FUra in bone marrow. The main difference observed between rapid injection and slow infusion in the kinetics of the drug was the very high level of 5-FUra reached by rapid injection in plasma and bone marrow, which was of short duration (min) when compared to the low sustained levels observed during infusion. This route-dependent pharmacokinetic profile is consistent with the reported absence of myelosuppression in prolonged infusion and may be related to the resultant lower levels of 5-FUra achieved in bone marrow.

5 FU infusion with mitomycin-C vs. 5 FU infusion with methyl-CCNU in the treatment of advanced upper gastrointestinal cancer: a Southwest Oncology Group Study.

A randomized trial was conducted by the Southwest Oncology Group (SWOG) in advanced carcinoma of the stomach and pancreas. Patients were assigned to receive monthly 5-fluorouracil 96-hour continuous infusions with either bolus mitomycin-C or oral methyl-CCNU. Mitomycin-C and methyl-CCNU were administered every eight weeks. The 5 FU-mitomycin combination produced a 14% and 22% response rate in disseminated stomach and pancreatic carcinoma, respectively. The combination of infusion 5 FU and methyl-CCNU achieved responses in 9% and 5% of stomach and pancreatic tumors, respectively. There was no significant difference in survival between limbs for either tumor. Median survival in gastric carcinoma on the 5 FU-mitomycin regimen was 25 weeks vs. 18 weeks on the 5 FU-METHYL-CCNU arm. In pancreatic carcinoma median survival on the mitomycin limb was 19 weeks as compared to 17 weeks on the methyl-CCNU program. Leukopenia was greater for the first course on the mitomycin limb. Regression analysis demonstrated that performance status was the most important pretreatment characteristic for predicting survival in both tumors. Neither 5 FU infusion combination appears to significantly alter the dismal prognosis of advanced upper gastrointestinal neoplasms.

Phase II evaluation of ftorafur in previously untreated colorectal cancer: a Southwest Oncology Group Study.

Eighty-four previously untreated patients with metastatic adenocarcinoma of the large intestine received intravenous ftorafur at a dosage of 2.25 g/m2/day for 5 consecutive days. Courses were repeated every three weeks. Regressions were noted in 9 of 84 treated patients (11%). Median survival for all patients was 32 weeks. Responders survived only 5 weeks longer than nonresponders; 36 vs. 31 weeks. Central nervous system toxicity was a limiting factor occurring in one-third of patients. Ftorafur in a daily X5 schedule appears not to make a significant contribution to the management of disseminated colorectal cancer.

Clinical trial of rubidazone in advanced squamous cell carcinoma of the lung and adenocarcinoma of the large intestine.

Sixteen patients with disseminated squamous cell carcinoma of the lung and 26 patients with adenocarcinoma of the colon and rectum were given rubidazone. Only one partial remission was observed in a previously untreated patient who had local recurrence of a rectal adenocarcinoma. The main toxic effects observed in previously treated patients consisted of leukopenia and thrombocytopenia. Also observed were anorexia, nausea, vomiting, alopecia, fever, and chills. Cardiotoxicity was observed in one patient after a total dose of 720 mg/m2 of rubidazone. It is concluded that rubidazone is a relatively inactive compound in the management of these two diseases.

5FU infusion with mitomycin-C versus 5 FU infusion with methyl-CCNU in the treatment of advanced colon cancer: a Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) in a randomized trial evaluated 5FU infusions in combination with either Mitomycin-C or Methyl-CCNU in patients with disseminated large bowel cancer. A response rate of 18% was noted on the 5FU-Mitomycin limb as compared to 16% on the Methyl-CCNU arm (p = .39). Median survival for all treated patients was 43 weeks on both arms. Myelosuppression was found to be more significant on the Mitomycin-C arm. Regression analysis demonstrated that performance status, sex, and primary site were significant pretreatment characteristics for predicting survival. The response rates associated with this burdensome method of 5FU administration in combination with either Mitomycin-C or Methyl-CCNU appear to offer little advantage over bolus 5FU alone.

Phase II trial of ftorafur with mitomycin C versus ftorafur with methyl-CCNU in untreated colorectal cancer.

In an attempt to substitute ftorafur for burdensome 5-fluorouracil (5-FU) infusions, 52 previously untreated patients were randomized to receive ftorafur with either mitomycin C or methyl-CCNU. Ftorafur was administered monthly as a 2-hour infusion daily x 5 days. Mitomycin C and methyl-CCNU were repeated every 8 weeks. A response rate of 27% (seven responses among 26 patients) was demonstrated on the mitomycin C arm compared to a response rate of 15% (four responses among 26 patients) on the methyl-CCNU arm (P = 0.25). There was no significant difference in the median survival between treatment arms. Central nervous system toxicity occurred in greater than 30% of the patients and appeared to be the limiting factor with ftorafur administration. Alternate schedules of ftorafur should be explored since there appears to be little advantage of a daily ftorafur schedule over conventional 5-FU infusions.

Mitomycin-C alone and in combination with infused 5-fluorouracil to the treatment of disseminated gastrointestinal carcinomas.

One hundred and thirty-two previously untreated patients with metastatic adenocarcinoma of the gastrointestinal (GI) tract were randomized to receive either a 120-hr infusion of 5-fluorouracil (5FU) with mitomycin-C or mitomycin-C alone. Superiority of the combination treatment was demonstrated with remissions in 30 out of 82 (37%) patients versus 9 out of 50 (18%) with the single drug treatment (P = 0.02). The median survial with 5FU--mitomycin-C was 29 weeks, as opposed to 20 weeks with mitomycin-C alone (P = 0.03). The combination produced significantly more severe myelotoxicity than the single drug, and jaundiced patients experienced more myelosuppression than non-jaundiced patients with both treatments.

Combined therapy for cancer of the anal canal: a follow-up report.

We believe this preoperative combined therapy is highly effective in treating squamous-cell carcinoma of the anal canal, and that a subsequent larger cooperative study with controls is indicated. This pilot study suggests that some individuals may be spared abdominoperineal resection when treated in the manner described.

Phase I trial of ftorafur combined with mitomycin C or methyl-CCNU in gastrointestinal cancers.

Twenty-five patients with disseminated gastrointestinal malignancies were treated in a phase I study with a combination of ftorafur and mitomycin C or florafur and methyl-CCNU. Most patients had been heavily treated previously. Gastrointestinal, central nervous system, and marrow toxicity were manageable. Tumor regression was noted in five of 25 patients. A large-scale phase II study in untreated patients with gastrointestinal malignancies appears indicated with a combination of these agents.

Hepatic artery infusion of 5-FUDR after prior systemic 5-fluorouracil.

Twenty-one patients with disseminated colon carcinoma and clinically significant liver metastases were treated with 5-FUDR via hepatic artery infusion (HAI). All patients had previously received systemic chemotherapy consisting of either 5-fluorouracil aone or in combination with other agents. At the time of the initiation of the HAI, clinical disease in all patients was progressing. A PR of hepatic metastases was noted in eight patients (35%) with a median and mean duration of response of 4.5 and 5.0 months respectively. The median and mean survival from the start of HAI for responders was 8.0 and 9.0 months and for nonresponders was 1.0 and 1.6 months respectively. It appears that a significant response rate can be achieved with HAI of 5-FUDR in spite of previous exposure to fluorinated pyrimidines.