ABSTRACT
Controlled-release oral formulations of oxycodone and morphine are both suitable analgesics for moderate to severe pain. They were compared in cancer-pain patients randomized to double-blind treatment with controlled-release oxycodone (n = 48) or controlled-release morphine (n = 52) every 12 h for up to 12 days. Stable analgesia was achieved by 83% of controlled-release oxycodone and 81% of controlled-release morphine patients in 2 days (median). Following titration to stable analgesia, pain intensity (0=none to 3=severe) decreased from baseline within each group (p
ABSTRACT
Datelliptium acetate (NSC 311152) is a water soluble analogue of ellipticine. It is a solid tumor selective compound. In vitro, in a disk diffusion, soft agar colony formation assay (25 micrograms/disk), the compound demonstrated solid tumor selectivity (compared to leukemia L1210) against colon adenocarcinoma 38 and pancreas ductal carcinoma 03. Upon intravenous administration, NSC 311152 was effective in vivo against a variety of murine solid tumors. Responses at maximum tolerated doses were: colon #07/A (T/C = 33%); 0.60 log cell kill), #38 [T/C = 0%; 4.2 log cell kill), colon #51/A (T/C = 2%; 1.2 log cell kill), undifferentiated colon #26/A (T/C = 38%; 0.4 log kill), mammary #16/C (T/C = 10%; 1.7 log cell kill), and pancreatic ductal carcinoma #03 (T/C = 0%; 80% cures through day 38). It was ineffective against pancreas #02 (T/C = 45%), mammary 17/A (T/C = 53%), and 17/A/ADR (T/C = 52%). At efficacious doses acute neurotoxicity (i.e. stupor and lethargy) and weight loss were noted (with rapid recovery from both toxicities). There were no delayed toxicities. The agent was slightly necrotizing and produced pain on SC injections. In lieu of its preclinical efficacy and toxicity profiles, we recommend further clinical investigation of this agent.
Subject(s)
Ellipticines/pharmacology , Neoplasms, Experimental/drug therapy , Adenocarcinoma/drug therapy , Animals , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Colonic Neoplasms/drug therapy , Drug Screening Assays, Antitumor , Ellipticines/administration & dosage , Ellipticines/toxicity , Female , Humans , Injections, Intravenous , Leukemia L1210/drug therapy , Male , Mammary Neoplasms, Experimental/drug therapy , Mice , Mice, Inbred Strains , Neoplasm Transplantation , Pancreatic Neoplasms/drug therapyABSTRACT
Batracylin (NSC 320846) is a water insoluble, solid tumor active compound discovered by the Development Therapeutics Program of the National Cancer Institute (NCI). In vivo, the NCI found this compound to be highly active [median treated tumor mass/median control tumor mass (T/C) = 0 to 20%] both orally and intraperitoneally against colon 38. In a disk diffusion, soft agar colony formation assay (500 ug/disk), we found solid tumor selectively (compared to leukemia L1210) against colon adenocarcinoma 38 (0-170 zu:L1210 leukemia; greater than 950 zu:C8), colon adenocarcinoma 9 (0-170 zu:L1210; greater than 950 zu:C9), colon adenocarcinoma 7/A (0-170 zu:L1210; 250-400 zu:C7), and pancreas ductal carcinoma 03 (0-170 zu:L1210; greater than 950 zu:Panc 03 (200 zone units [zu] = 6.5 mm zone of inhibition of cultured tumor colonies from drug disk). In vivo we have tested batracylin against mammary adenocarcinoma 16/C, colon 9, colon 38, colon 51, Panc 03, and hepatoma 129. Upon oral administration, batracylin was effective against colon 9 (T/C = 2.4%) and marginally active against colon 38 (T/C = 39%). Batracylin was orally ineffective against Panc 03 (T/C greater than 100%), colon #51 (T/C = 77%) and hepatoma 129 (T/C greater than 100%). Upon subcutaneous administration, batracylin was effective against colon #9 (T/C = 0%), and Panc 03 (T/C = 15%) but ineffective against mammary 16/C (T/C greater than 100%). At efficacious doses, delayed neurotoxicity, hepatic toxicity and a significant host weight loss was noted (with slow recovery). Both our in vitro data and the NCI in vivo data confirm its scant activity against L1210 (%ILS = 8 to 16%). Although showing activity against selected murine solid tumors, it lacked curative potential with early stage disease [C38, C9, Panc 03] and has shown relative inactivity in vitro against human solid tumor cell lines (H-125, CX-1, HCT-8, HCT-116). Batracylin has entered large animal toxicology trials at the NCI, anticipating phase I clinical evaluation.
Subject(s)
Antineoplastic Agents/therapeutic use , Neoplasms, Experimental/drug therapy , Quinazolines/therapeutic use , Adenocarcinoma/drug therapy , Animals , Antineoplastic Agents/adverse effects , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Cell Survival/drug effects , Cells, Cultured , Colonic Neoplasms/drug therapy , Drug Administration Schedule , Drug Screening Assays, Antitumor , Humans , Mammary Neoplasms, Experimental/drug therapy , Mice , Mice, Inbred Strains , Pancreatic Neoplasms/drug therapy , Quinazolines/adverse effects , Tumor Cells, CulturedABSTRACT
5-FUra is a familiar member of a variety of clinically useful regimens. Examples include: Cytoxan-Adriamycin-5-FUra (CAF); Methotrexate-Prednisone-Vincristine-Cytoxan-5-FUra (the Cooper regimen); and CisDDPt-5-FUra. In addition to its clinical utility, over 20 different 5-FUra-combinations have been reported to be therapeutically synergistic in experimental systems. In this report, we will attempt to evaluate the reasons behind the widespread utility of this agent in combination therapy and suggest future directions for research efforts.
