melphalan and Digestive-System-Neoplasms

Regionally advanced cancer is a common, often unresolved problem. Effective local control with chemotherapy is limited by the toxicity following systemic administration. Chemofiltration (CF) is a form of regional perfusion that enables the administration of cytotoxic drugs into one body area while limiting systemic toxicity. The drug is infused into the artery supplying the involved area. The venous effluent of the same organ is pumped out into a hemofiltration unit at a high flow rate. The drug is then filtered away and the blood returned to systemic circulation.. Forty-one patients underwent 45 CF. Twenty-four patients had CF of the pelvis for advanced rectal carcinoma (10), malignant melanoma (6), and cancers of the uterine cervix (3), ovary (2), vulva (1), endometrium (1), and anus (1). Seventeen patients underwent CF of the liver for metastatic colon (10), breast (4), pancreas (1), ovary (1), and unknown primary (1) cancer. 5-fluorouracil (1 g/m2) and mitomycin-C (30 mg/m2); cisplatinum (200 mg/m2) alone or combined with bleomycin (50 mg/m2) and mitomycin-C (20 mg/m2); or melphalan (1 mg/kg) were the combinations used.. Generally the procedure was well tolerated. Complications included transient leukopenia (18), paralytic ileus (2), hair loss (2), renal failure (1). Two patients died within 40 days following CF. Of 36 evaluable patients, 16 (44%) had partial response, 14 (38%) had stable disease, and 6 (18%) had disease progression. A decrease of at least 30% in carcinoembryonic antigen levels occurred in 12 of 24 patients (50%). Median time to progression was 7 months. Ten of 13 patients (77%) achieved good symptomatic palliation.. The results of CF in our study are not superior to alternative methods of drug delivery to the liver and pelvis. However, considering that previous systemic chemotherapy had failed two-thirds of the patients, some benefit may be attributed to this regional delivery modality. Furthermore, pelvic CF afforded very significant symptomatic relief which was definitely superior to other methods.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Renal Cell; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Digestive System Neoplasms; Female; Fluorouracil; Genital Neoplasms, Female; Hemofiltration; Humans; Kidney Neoplasms; Male; Melanoma; Melphalan; Middle Aged; Mitomycin; Prognosis; Survival Rate

Topics: Administration, Oral; Antineoplastic Agents; Digestive System Neoplasms; Drug Combinations; Fluorouracil; gamma-Globulins; Humans; Immunotoxins; Melphalan; Portal System

At the UCSD Cancer Center several chemotherapeutic agents have been evaluated for safety and clinical utility when delivered by the intraperitoneal route. Both melphalan and cytarabine have demonstrated a major pharmacokinetic advantage for peritoneal cavity exposure to drug compared to that of the plasma when these agents are administered directly into the abdominal cavity. In addition, limited clinical efficacy for both agents has been demonstrated. In one experimental system cisplatin and cytarabine have shown significant concentration-dependent synergy. As intraperitoneal drug delivery allows one to administer extremely high concentrations of chemotherapeutic agents to tumors localized to the abdominal cavity, this therapeutic approach is perhaps the optimal method for producing clinically relevant concentration-dependent drug synergy. Patients with refractory ovarian carcinoma and other tumors principally confined to the peritoneal cavity have demonstrated subjective and objective improvement following intraperitoneal therapy with a cisplatin-cytarabine-based chemotherapeutic regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytarabine; Digestive System Neoplasms; Doxorubicin; Drug Evaluation; Female; Humans; Infusions, Parenteral; Male; Melphalan; Middle Aged; Ovarian Neoplasms; Peritoneal Cavity