trimethoprim--sulfamethoxazole-drug-combination and Carcinoma--Small-Cell

The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support.

Topics: Administration, Oral; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Endpoint Determination; Etoposide; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Ifosfamide; Lung Neoplasms; Male; Middle Aged; Prognosis; Survival Rate; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vindesine

The efficacy of the prophylactic administration of sulfamethoxazole/trimethoprim (ST) plus norfloxacin (NFLX) versus ST alone to prevent the development of bacterial infection during chemotherapy-induced leukopenia was compared in patients with lung cancer. Patients who underwent systemic chemotherapy were randomized into one of the prophylactic regimens when grade 3 or 4 leukopenia occurred. Prophylactic treatment was performed on 133 courses of leukopenia in 75 patients and the efficacy was evaluated on 127 of those courses after excluding those patients who demonstrated a fever within 24 h from the start of the prophylaxis. The number of patients who had leukopenia associated fever was two out of 63 (3.2%) with the ST plus NFLX regimen and 10 out of 64 (15.6%) with ST alone; the difference was statistically significant. The prophylactic use of ST plus NFLX was thus found to be more useful than ST alone for the treatment of chemotherapy-induced leukopenia in patients with lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cisplatin; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Norfloxacin; Trimethoprim, Sulfamethoxazole Drug Combination

In 103 patients with small-cell lung cancer, we compared four courses of standard doses of Adriamycin (A) (Adria Laboratories, Columbus, Ohio), vincristine (V), and cyclophosphamide (C) with a regimen of increased doses of cyclophosphamide and to a lesser extent, Adriamycin. We found no significant difference in rate (22% v 21%) or median duration (seven v nine months) of complete remission. Patients not in complete remission after the four cycles of AVC received two courses of VP-16 (etoposide) and cisplatin: the complete remission rate increased to 49% and 48% respectively. Patients on the high-dose arm received co-trimoxazole prophylaxis; those on the standard arm did not. Patients on the high-dose arm had a higher incidence of neutropenia (nadir less than 500 cells/microL) but a lower incidence of infection for similar degrees of neutropenia. However, they also suffered more severe side effects of a different kind. Cotrimoxazole thus allowed for the administration of higher doses of chemotherapy to outpatients by protecting them from infection. However, the higher doses of cyclophosphamide and Adriamycin, did not improve treatment results, produced more severe side effects, and is not recommended.

Topics: Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cats; Cisplatin; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Combinations; Etoposide; Female; Humans; Infection Control; Lung Neoplasms; Male; Middle Aged; Nausea; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vincristine; Vomiting

Topics: Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Small Cell; Ceftriaxone; Cisplatin; Combined Modality Therapy; Cranial Irradiation; Etoposide; Fatal Outcome; Female; Humans; Immunocompromised Host; Lung Neoplasms; Opportunistic Infections; Pneumonia, Pneumocystis; Pneumonia, Staphylococcal; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Fifteen patients undergoing intensive chemotherapy for oat cell carcinoma of the lung in a protected environmental unit received antimicrobial prophylaxis with oral trimethoprim-sulfamethoxazole and short courses of parenteral ticarcillin, tobramycin, and miconazole. Altogether, 58 (65%) of 89 strains of aerobic bacteria and 28 (60%) of 47 strains of anaerobic bacteria present before prophylaxis were no longer cultured from stool specimens during prophylaxis. Ten strains of bacteria and four fungi were acquired in the stools during prophylaxis. Most fungi persisted in the throat and stools during prophylaxis. Bacterial infections occurred infrequently, but three patients developed Candida esophagitis. The regimen was well tolerated with minimal side effects.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacteria; Bacterial Infections; Carcinoma, Small Cell; Digestive System; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Miconazole; Middle Aged; Sulfamethoxazole; Ticarcillin; Tobramycin; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination