ABSTRACT
Novobiocin, a commercially available oral antibiotic, inhibits DNA topoisomerase II in a manner shown in cell culture to enhance the cytotoxicity of alkylating agents and cisplatin. Thirty-six patients were entered on a Phase II trial using high-dose cisplatin (100 mg/m2 on days 1 and 8 for four cycles) after steady-state dosing with novobiocin (1000 mg or four 250-mg capsules every 12 hours for six doses, four of which were administered before each dose of cisplatin). One patient remains on study and cannot be evaluated for response. No complete responses were seen. Three patients (8%) had partial responses and an additional patient had an unconfirmed partial response. The median survival time of all patients was just less than 7 months. These results are comparable with those of other concurrent Southwest Oncology Group (SWOG) Phase II and III trials of high-dose cisplatin in non-small cell lung cancer (NSCLC). Novobiocin plasma levels were obtained for three patients and were approximately 50% of the optimal concentration as reported in cell culture for potentiation of cytotoxicity. It was concluded that an optimum test of novobiocin as a modulator of cytotoxicity may require the availability of an intravenous preparation.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/administration & dosage , Lung Neoplasms/drug therapy , Novobiocin/administration & dosage , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capsules , Cisplatin/adverse effects , Drug Evaluation , Female , Humans , Infusions, Intravenous , Kidney/drug effects , Male , Middle Aged , Novobiocin/adverse effects , Novobiocin/blood , Remission Induction , Southwestern United StatesABSTRACT
Two cases of pseudomembranous colitis are presented. The first patient had been treated with novobiocin-tetracycline and penicillin, and two weeks later developed severe fulminating diarrhea with ascites and bilateral pleural effusions which did not respond to intravenous ACTH. Subsequently she underwent subtotal colectomy and made a rapid and complete recovery. The second patient developed severe diarrhea two weeks after a 10-day course of clindamycin. She was treated with intravenous ACTH, oral Lactobacillus and a fecal enema and made a complete recovery.These cases reconfirm the importance of antibiotics as etiologic agents in this disease. They also stress the classic sigmoidoscopic and histologic findings that should facilitate prompt and rapid diagnosis.