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Biomedical subjects

R A Fleming

Publications and source records attributed to R A Fleming.

60 records · Page 4Linked to original sources
PubMedDate not supplied

Cytologic assessment before and after intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis.

OBJECTIVE: A phase I/II clinical trial of surgical cytoreduction combined with intraperitoneal hyperthermic chemotherapy (IPHC) for patients with disseminated peritoneal carcinoma was begun in December 1991. The use of peritoneal cytology to assess this treatment modality was the objective of this study. STUDY DESIGN: Adult patients with primary intraabdominal cancer with peritoneal dissemination underwent surgical debulking and intraoperative, two-hour, heated abdominopelvic perfusion with mitomycin C (MMC). Peritoneal washings were sent before and after IPHC, and the use of peritoneal cytology in this setting was reviewed retrospectively. RESULTS: Twenty patients (9 female, 11 male) with adenocarcinoma (19) and one with epithelial mesothelioma, all with bulky peritoneal disease, were treated. Pre- and post-IPHC cytologic specimens were available for 18 cases. Cytology was tumor negative in three cases before and after IPHC. Conversion to negative post-IPHC cytology was seen in 6 of 15 cases and correlated with total or near-total tumor debulking (Fisher's exact test, P = .002). For 13 patients with follow-up > or = 6 months, 6 patients with both negative post-IPHC cytology and tumor < or = 1 g were alive at 6 months; of 7 patients with residual gross tumor or positive post-IPHC cytology, 5 had died within 6 months (P = .02). CONCLUSION: Some patients undergoing IPHC with tumor-positive peritoneal cytology will convert to negative cytology following IPHC. This correlates with total or near-total tumor debulking and is associated with improved survival.

Adult↗
PubMedDate not supplied

An overview of cyclophosphamide and ifosfamide pharmacology.

Cyclophosphamide and ifosfamide are alkylating agents administered to treat malignant disease. They are prodrugs and require activation by hepatic microsomal enzymes before being metabolized to their respective cytotoxic species, phosphoramide mustard and ifosfamide mustard. These species alkylate DNA, forming DNA-DNA cross-links that result in inhibition of DNA synthesis and cell death. Resistance to oxazaphosphorines is poorly understood, although increased aldehyde dehydrogenase activity may be a significant factor. Although both compounds share a common metabolic pathway, 4-hydroxylation of ifosfamide occurs at a slower rate and to a lesser extent than that of cyclophosphamide. This difference significantly alters the toxicity profile of ifosfamide. Leukopenia is the dose-limiting toxicity of cyclophosphamide, and neurotoxicity is the dose-limiting toxicity of ifosfamide when preventive measures are taken to reduce urotoxicity. With recent findings concerning their basic and clinical pharmacology, the therapeutic index of these compounds can be improved.

Animals↗