ABSTRACT
Fifty-three patients with histologically proven ovarian cancer were treated with intraperitoneally administered cisplatin or human recombinant interferon-alpha through a totally implanted peritoneal access port. A total of 281 treatment courses were given. No complications related to surgical implantation of the port were seen. Infectious complications, intra-abdominal problems or subcutaneous drug extravasation did not occur. In two patients the number of treatment courses was limited due to inflow obstruction. A totally implanted peritoneal access port proves to be a reliable route for the intraperitoneal treatment of patients with ovarian cancer. The strict aseptic technique we used contributes to its safety by preventing intra-abdominal infections.
ABSTRACT
A consecutive phase I and phase II study of a 14-days continuous infusion schedule of 5-fluorouracil with weekly bolus injection leucovorin was performed in 10 and 21 patients, respectively. Chemotherapy courses were repeated every 4 weeks. 1 patient in the phase I study was pretreated, all the others had no prior chemotherapy. 300 mg/m2 continuous infusion of 5-fluorouracil for 14 days could not be combined with any dose of leucovorin 20-200 mg/m2 without severe toxicity, mainly gastrointestinal. A 5-fluorouracil dose of 200 mg/m2 day for 2 weeks, combined with weekly bolus injection of 200 mg/m2 leucovorin was found to be feasible. The phase II study was performed at this dose level. In 21 patients a response rate of 5/21 [23.8%, 95% confidence interval (CI) 8.2-47.1%] was observed, and the overall response rate was 8/29 (27.6%, 95% CI 12.7-47.2%). Responses were observed in patients with liver (4), lung (1), abdominal (1), and multiple (2) metastases. Median survival was 14.5 months. Toxicity was low, mucositis WHO grade 1-2 being most frequent (36/113 courses = 31.9%). Patients' acceptance of this continuous infusion schedule was generally good.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Adult , Aged , Colorectal Neoplasms/secondary , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Evaluation , Drug Synergism , Drug Therapy, Combination , Female , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Leucovorin/adverse effects , Male , Middle AgedABSTRACT
The modulating effect on drug resistance of amiodarone (AM) and its metabolite desethylamiodarone (DEA) was studied in a P-glycoprotein-positive human colon carcinoma cell line COLO 320, and a human small-cell lung carcinoma cell line GLC4 and its adriamycin (Adr)-resistant subline GLC4-Adr (both P-glycoprotein-negative). AM, DEA and verapamil induced an increase in cytotoxicity of Adr, vincristine and etoposide (VP16) in COLO 320 cells, while in the GLC4 and GLC4-Adr cell line no effect was seen. In the COLO 320 cell line, AM caused more intracellular, and especially intranuclear, fluorescence of Adr and more Adr-induced DNA strand breaks as compared to Adr alone. Moreover, an increase in VP16-induced topoisomerase II-DNA complexes was observed when AM was added. Competition between AM and Adr for the same efflux pump was suggested in efflux studies. The colony-forming unit granulocyte macrophage (CFU-GM) assay showed no increase in cytotoxicity of Adr when AM was added. Fourteen patients with Adr-resistant tumors were treated with Adr and AM. In these patients, peak serum levels of AM plus DEA of 10 microM were reached. Patient serum (20%) obtained after the first i.v. AM infusion induced in vitro significantly more cell kill of Adr in COLO 320 cells. Apart from a transient first-degree AV block in one patient, no cardiac toxicity was observed with the combination of Adr and AM. Bone-marrow toxicity was the same as expected from Adr alone in these patients. One of the 13 evaluable patients obtained a partial remission.
Subject(s)
Amiodarone/pharmacology , DNA Damage , Doxorubicin/pharmacology , Drug Resistance , Etoposide/pharmacology , Neoplasms/drug therapy , Vincristine/pharmacology , Adult , Amiodarone/metabolism , Amiodarone/therapeutic use , Biological Transport/drug effects , Carcinoma, Small Cell , Cell Line , Cell Survival/drug effects , Colonic Neoplasms , Doxorubicin/metabolism , Doxorubicin/therapeutic use , Drug Screening Assays, Antitumor , Female , Humans , Kinetics , Lung Neoplasms , Male , Tumor Stem Cell AssayABSTRACT
170 patients were treated with continuous infusion of epirubicin, mitoxantrone, carboplatin or 5-fluorouracil through an implanted venous access port with a portable infusion pump. A total of 440 cycles were given on an outpatient basis. The patients were instructed how to dissolve their drugs and to change the syringes. The complication rate was low. 10 patients developed a thrombosis of the subclavian vein, resulting in cessation of therapy in 5. Pulmonary embolism occurred twice, in 1 patient during a period of subclavian vein thrombosis. Needle dislocation occurred 6 times and catheter occlusion 20 times. Patency was restored with saline or urokinase. Local infection occurred 3 times and systemic infection only once. This technique is suitable for continuous infusion of different cytostatic drugs on an outpatient basis. Patients were able to prepare their drugs at home and the system can remain in situ for 3 weeks without increasing the complication rate.
