Genitourinary Medicine staff knowledge about the risks of specific sexual behaviours in the transmission of HIV.

The aim of this study was to investigate the consistency of information about HIV sexual transmission provided by genitourinary medicine (GUM) staff to their patients. This staff group's knowledge of specific sexual risk behaviours was obtained using a self-administered anonymous 21-item questionnaire. Results for 106 respondents revealed considerable inconsistency amongst GUM staff's risk ratings of different sexual activities. These inconsistencies in risk ratings were significantly related to profession and gender. The results are discussed in terms of the lack of available consistent information about oral sex as well as less conventional sexual activities. The results support the need for a strategy to ensure the provision of clear and consistent messages about the sexual transmission of HIV. Any sexual health promotion strategy within GUM clinics needs to review and audit the quality of information given by health professionals to patients.

Upholsterers' glue associated with myocarditis, hepatitis, acute renal failure and lymphoma.

A 20-year-old man with heavy exposure to upholsterers' glue presented with life-threatening acute myocarditis, and then rapidly developed acute hepatic necrosis and acute renal failure. He made a rapid and complete recovery from this florid acute illness, only to present three months later with supradiaphragmatic non-Hodgkin's lymphoma. These illnesses have all been described in association with solvent exposure. The unique feature of this case is the occurrence of multiple manifestations which might be attributed to solvent exposure, both acute and chronic, in the same individual.

Carboplatin and continuous infusion 5-fluorouracil for advanced head and neck cancer.

Fifty-one patients with recurrent or advanced squamous cell carcinoma of the head and neck received carboplatin 70 mg/m2/day bolus X 5 days i.v. and 5-fluorouracil (5-FU) 1000 mg/m2/day by continuous infusion i.v. for 5 days as initial chemotherapy. There were four complete responders (CR) and 12 partial responders (PR). Durations of CR were 6.8 months, 7.2+ months and 14.8+ months with one patient lost to follow up after achieving CR. For objective responders the median relapse-free survival from the time of response was 5.3 months and survival from registration 11.7 months. The median survival for all patients was 4.8 months. The major toxicities were myelosuppression and mucositis. Neutropenia (less than 1.0 X 10(9)/l) occurred in 19% of patients, thrombocytopenia (less than 50 X 10(9)/l) in 17% and severe (WHO grade three or four) mucositis was experienced by 28% patients. This combination had less gastrointestinal and nephrotoxicity than platinum containing combinations and can be used in patients with a poorer performance status.

Carboplatin (CBDCA, JM-8) and VP-16-213 in previously untreated patients with small-cell lung cancer.

The efficacy and toxicity of carboplatin 100 mg/m2, administered intravenously (IV) daily X 3, and VP-16-213 120 mg/m2, IV daily X 3, administered every 28 days for six courses, was assessed in 94 (36 limited stage, 58 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to all limited-stage patients with a complete (CR) or partial response (PR) after three chemotherapy courses. Cranial irradiation was administered to all patients with CR. Objective responses were seen in 77% (CR 40%, PR 37%) of patients with limited-stage and 58% (CR, 9%; PR, 49%) with extensive-stage disease. Median relapse-free survival for objective responders with limited stage was 14.6 months and 7.9 months for extensive-stage patients. Median relapse-free survival following CR was 15.4 months and 8.5 months for PR. Median survival was 15.3 months for limited-stage and 8.1 months for extensive-stage patients. The combination was well tolerated with mild nausea or less (World Health Organization [WHO] grade 0 or 1) in 62% of patients and minimal mucositis, renal, neurotoxicity, or ototoxicity. Neutropenia less than 1.0 X 10(9)/L (WHO grade 3 or 4) was seen in 63% of patients, with two deaths from infection while neutropenic. The combination of carboplatin and VP-16-213 is a new, active program with low toxicity when applied intensively in previously untreated patients with small-cell lung cancer.

Randomised study of ticarcillin, cefamandole with or without tobramycin in febrile, neutropenic patients with solid tumors.

A prospective randomised study was conducted comparing the efficacy and toxicity of the antibiotics ticarcillin and cefamandole (TC) with or without tobramycin (TCT) in 100 febrile neutropenic patients with solid tumours undergoing conventional chemotherapy. In this study, neutropenia less than 100/microliter was noted in 31% of 106 evaluable infectious episodes and neutrophil counts less than 1,000/microliter persisted for a median 4 days. Infection was microbiologically documented in 42% of episodes (bacteremia 24%) with gram-negative organisms responsible for 63% of bacterial isolates. Overall, 65% of episodes responded to TC and 76% to TCT (p greater than 0.05). Patients with initial shock bacteremia, pulmonary infection, or gram-negative sepsis responded relatively poorly. Neutrophil nadir and pathogen susceptibility did not influence outcome. Antibiotic toxicity was minimal with no tobramycin-related nephrotoxicity. These results are broadly comparable to those observed with leukemic patients, but the relatively short duration of neutropenia in the solid-tumour patients appears to minimize the need for additional antibiotics provided there is adequate antimicrobial coverage with the initial choice of antibiotics.

Multiple sequential biomarkers in monitoring patients with carcinoma of the lung.

To correlate serial biomarkers and disease activity in carcinoma of the lung, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), adrenocorticotropic hormone (ACTH), C3-derived protein (C3DP-C), and LDH were assayed in 43 patients with small cell lung carcinoma (SCLC) and in 20 patients with non-small cell lung cancer (NSCLC) (15 with adenocarcinoma, three with squamous cell carcinoma, and two with mixed histology). Disease status after treatment was rated as one of the following: complete response, partial response, minor regression, stable disease, and progressive disease. Significant correlations between disease status and markers in SCLC were found for CEA, NSE, LDH, and ACTH. In NSCLC, only CEA and LDH showed significant correlation. Marker-marker correlations were significant in SCLC for CEA and NSE (P less than 0.05), CEA and LDH (P = 0.01), and NSE and LDH (P less than 0.01); in NSCLC none were significant. None of the markers exhibited significant correlations with specific metastatic sites. Certain biomarkers (CEA, NSE, and LDH in SCLC; CEA and LDH in NSCLC) can be used alone or in combination to monitor disease activity but appear to be no more sensitive than standard clinical investigational methods.

High-dose methotrexate with leucovorin rescue, vinblastine, and bleomycin with or without tamoxifen in metastatic renal cell carcinoma.

A regimen of high-dose methotrexate with leucovorin rescue, vinblastine, and bleomycin with or without tamoxifen was administered to 34 patients with metastatic renal cell carcinoma. No complete remissions were observed, but ten patients (30%) achieved partial remission and an additional 13 patients (39%) had stabilization of disease. The median survival of responding patients (110 weeks) was significantly longer than that of nonresponding patients. The addition of tamoxifen did not influence response or survival. This regimen was tolerated without significant toxicity. A prospective randomized study of the vinblastine and high-dose methotrexate regimen compared to the respective single agents seem to be indicated.

Value of prophylactic cranial irradiation given at complete remission in small cell lung carcinoma.

The optimal use of "prophylactic" cranial irradiation (PCI) in patients with small cell lung cancer remains undetermined. This study reviews the impact of PCI, given at complete remission (CR), on neurologic relapse in 172 consecutive patients with small cell lung cancer treated in three sequential chemotherapy protocols at the University of Maryland Cancer Center. In the first study of 38 patients, none received PCI. In the second study of 109 patients, the first 28 achieving CR were randomized to 3000 rad of PCI in ten fractions (PCI+) or to observation (PCI-). Thereafter, based on interim analysis, all patients achieving CR received PCI. In the third study, to date, 25 patients achieving CR have received PCI. Overall, 169 patients were evaluable for neurologic relapse, and 30 of 90 patients achieving CR received PCI. Among all patients with CR, with adjustment for disease extent, there was a significant delay to any neurologic relapse (P = 0.01) and cerebral metastases (P = 0.02) for PCI+ compared to PCI- patients. Among PCI- patients with CR, cerebral metastases alone occurred in 28% as the sole site and in 33% as the initial site, whereas cerebral relapse occurred prior to systemic relapse in only one PCI+ patient with CR. Patient survival however, was not significantly altered by PCI. PCI at CR confers effective and worthwhile local control in the CNS, especially during periods of systemic response, and a small percentage of patients may benefit. Systemic drug resistance still determines overall survival.

Four-drug combination chemotherapy for advanced cervical carcinoma.

Thirty-one patients with advanced stage squamous cell carcinoma of the cervix were treated with the four-drug combination fluorouracil, doxorubicin, cyclophosphamide, and vincristine. Four patients achieved complete remission (13%) and 15 partial remission (45%). The only factor of adverse prognostic significance was poor initial patient performance. Median survival for the patients entering complete remission exceeded 54 weeks and was 43 weeks for patients achieving partial remission. Seven patients are still alive at 50 weeks. This represents a notable prolongation of survival compared with those patients who did not achieve remission. Toxicity for the combination was not excessive; myelosuppression and vincristine-induced neuropathy were the most prominent. These results are moderately encouraging and confirm the sensitivity of cervical carcinoma to systemic chemotherapy. Further studies to define the optimal use of chemotherapy in both advanced and earlier stages of disease are warranted.

Alternating non-cross-resistant combination chemotherapy for small cell anaplastic carcinoma of the lung.

The development of drug resistance limits the survival or patients with small cell anaplastic carcinoma of the lung (SCLC). The present study was undertaken to overcome this problem by administering two alternating noncross resistant combination chemotherapy regimens. One-hundred-one patients were entered on study, and 98 were evaluable, with a median onstudy time of 55+ weeks. All patients received the initial combination therapy of cyclophosphamide, methotrexate, and vincristine, alternating every three weeks with Adriamycin and VP16-213 (etoposide). Radiation therapy was not a standard part of protocol. Thirty-two patients had regional disease (LD), and 66 had extensive disease (ED). Overall, 76% of patients responded to this therapy with 30 (31%) complete remission (CR) and 44 (45%) partial remissions (PR); the respective CR and PR rates were 31% and 50% for LD, and 30% and 42% for ED patients. Myelosuppression was the principal toxicity with a leukocyte nadir of 2.0 X 10(9)/1 in 10% of cycles. Septicemia in six neutropenic ED patients with progressive disease contributed to the only treatment-related deaths. Patients entering CR had a median survival greater than 51 weeks (range, 8-150+); 58+ for LD and 49+ for ED patients. Patients in PR had respective median survivals of 33+ (overall), 43+ (LD), and 24+ (ED) weeks. Forty patients have had relapses with initial sites being local sites in 35%, and neurologic in 38%. Although this protocol has not discernibly delayed the onset of drug resistance, the problem should be considered when new protocols are designed in SCLC.

Significant factors in the optimal management of advanced stage germ cell carcinoma.

Twenty-two patients with advanced stage germ cell carcinomas received a combination chemotherapy regimen of cis-platinum, vinblastine, bleomycin and actinomycin D. There were 16 (73%) complete remissions, (five documented at surgery), one patient (5%) whose residual disease was completely resected and five (22%) partial remissions. The only adverse significant pretreatment factors were extent or bulk of initial disease and poor performance status. Prior radiotherapy or chemotherapy did not influence the potential to achieve complete remission, but was associated with increased haematological toxicity. Toxicities were common and there were three treatment related deaths, one from septicaemia and two from pulmonary fibrosis, emphasising the need for expertise and optimal supportive care when administering this complicated regimen. There was a significant survival advantage for the patients achieving disease-free status compared to partial responders (p = 0.02). Only one relapse has occurred among the former group with 82% alive and disease-free with follow-up of 27-50 months, indicating the majority of these patients may be cured. Management of advanced stage germ cell carcinoma can now be considered highly successful although further studies are needed to determine optimal treatment for patients with bulky disease and the role, if any, of maintenance therapy.

Meningeal carcinomatosis in small cell carcinoma of the lung.

Cerebral and meningeal metastases are increasingly important complications in small cell anaplastic carcinoma of the lung. In a study at this institution, 60 evaluable patients received intensive chemotherapy without prophylactic cranial irradiation or other prophylactic measures. The complete plus partial remission rate was 78 percent with a median survival of 49+ weeks (range eight to 106+ weeks) for those with a complete response and 18+ weeks (range six to 67 weeks) for those with a partial response, all of which are comparable to other reported series. In 11 patients (18 percent) meningeal carcinomatosis has developed. Forty-two percent of the patients with a relapse have exhibited meningeal carcinomatosis and in 27 percent of the patients with a relapse it was the only site of relapse. Cerebral metastases occurred in 27 percent of those who had a relapse, and in 12 percent this was the sole site of relapse. Simultaneous meningeal carcinomatosis and cerebral metastases occurred in 8 percent of the patients with a relapse. The median time to meningeal relapse was 27 weeks (range 12 to 60 weeks) compared with 25+ weeks (six to 106+ weeks) over-all, and the median survival was 28 weeks (range 14 to 82 weeks) compared with 25+ weeks (two to 106+ weeks) for the whole group with small cell carcinoma of the lung. Meningeal involvement in small cell carcinoma of the lung must now be considered a sanctuary site of equal importance to cerebral metastases. To prevent and treat this complication will necessitate evaluation of all available modalities, including cranial and spinal irradiation, intrathecal chemotherapy and systemic agents that readily cross the blood-brain barrier.

Haemolytic anaemia after cisplatin treatment.

Normochromic or normocytic anaemia is a common side effect of treatment with cisplatin. Two patients treated with cisplatin 100 mg/m2 in combination with vinblastine, bleomycin, and actinomycin D developed haemolytic anaemia. Neither patient had evidence of haemolysis before treatment, and in both cases severe haemolytic anaemia developed after several courses of cisplatin and when the cancer had regressed almost completely. The importance of haemolysis in the development of anaemia after cisplatin treatment has not been investigated fully and further studies are needed.

Triple drug chemotherapy for advanced ovarian carcinoma: comparative study of two regimens.

Two consecutive studies were undertaken in patients with advanced adenocarcinoma of the ovary to compare melphalan, adriamycin and 5-fluorouracil (MAF) with cyclophosphamide, adriamycin and 5-fluorouracil (CAF). Twenty-one patients received MAF and 19 received CAF. The objective response rate was 35% for MAF and 62% for CAF patients, and complete remission occurred in 23% of MAF, and in 56% of CAF, patients. These differences were not statistically significant. In both groups, complete remission had a statistically significant and favourable influence on survival. Toxic effects were predominantly haemopoietic and gastrointestinal, MAF having a significantly greater thrombocytopenic potential than CAF, but over-all tolerance was good on both protocols. MAF and CAF are comparable and effective combinations for the treatment of advanced ovarian cancer, but do not demonstrate superiority to single alkylating agent therapy or to other combinations. This emphasizes the continuing need for well designed randomized trials comparing single alkylating agents with combinations of known active agents.

Methyl-CCNU, 6-thioguanine, and 5-fluorouracil in advanced colorectal cancer.

Consecutive studies were undertaken in advanced colorectal adenocarcinoma, comparing two different schedules of the combination methyl-CCNU, 6-thioguanine, and 5-fluorouracil in 89 patients. The two schedules exhibited similar efficacies, with a combined complete and partial remission rate of 17%, a median response duration of 36+ weeks, and a median survival of 53+ weeks. Significant symptomatic benefit was seen in 52% of patients. Toxicity was predominantly hemopoietic and gastrointestinal, being acceptable overall, with only minor qualitative differences between the two protocols. These triple-drug regimens exhibit response rates and survival patterns comparable with those reported for other multidrug combinations and some single agents. It would appear that major improvements in the management of advanced-stage disease must await the availability of more efficacious agents used alone or in combination.

Cyclical combination chemotherapeutic regimen in adult soft tissue sarcoma.

A cyclical combination chemotherapeutic regimen of Adriamycin and cyclophosphamide alternating with actinomycin D and DTIC was administered to 20 evaluable patients with metastatic soft tissue sarcoma. Responses included four (20%) partial remissions and five (25%) patients with stable disease. There was a significant prolongation of survival for responding patients (median 42.5+ weeks) compared to patients with progressive disease (median 17.5 weeks). Principal toxicity was nausea and vomiting particularly with the actinomycin D/DTIC combination and four patients found this so intolerable they withdrew from study. These results are inferior to those reported for Adriamycin alone and other combinations. Further evaluation of the concept of sequential non-cross-resistant combinations would only seem appropriate if newer more active agents are identified and each combination is administered for a set duration before crossing over to the alternative regimen.