levoleucovorin and Hemolytic-Uremic-Syndrome

Phase II trials of combination chemotherapies have shown encouraging palliative benefit, objective response rates, and survival outcomes. Until ongoing phase III trials confirm these benefits, the current standard treatment for metastatic pancreatic adenocarcinoma remains single agent gemcitabine. The fixed rate infusion schedule of 10 mg/m2/min is gaining wide acceptance and is a promising investigational priority. A very reasonable alternative to single agent gemcitabine, and our bias, is enrollment into clinical trials evaluating novel gemcitabine-based combinations. Further investigation is needed to determine optimal incorporation of so-called targeted therapy with combination chemotherapy.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Camptothecin; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Deoxycytidine; Docetaxel; Enzyme Inhibitors; Epirubicin; Fluorouracil; Gemcitabine; Hemolytic-Uremic Syndrome; Humans; Interferon alpha-2; Interferon-alpha; Irinotecan; Leucovorin; Multicenter Studies as Topic; Organoplatinum Compounds; Paclitaxel; Palliative Care; Pancreatic Neoplasms; Recombinant Proteins; Respiratory Distress Syndrome; Taxoids; Treatment Outcome

The 24-hour continuous infusion of 5-fluorouracil (5-FU) and folinic acid (FA) as part of several new multidrug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective, with low toxicity. In a previous phase II study with 3-weekly bolus 5-FU, FA and mitomycin C (MMC) we found a low toxicity rate and response rates comparable to those of regimens such as ELF, FAM or FAMTX, and a promising median overall survival. In order to improve this MMC-dependent schedule we initiated a phase II study with high-dose 5-FU/FA and 3-weekly bolus MMC.. From February, 1998 to September, 2000 we recruited 33 patients with AGC to receive weekly 24-hour 5-FU 2,600 mg/m(2) preceded by 2-hour FA 500 mg/m(2) for 6 weeks, followed by a 2-week rest period. Bolus MMC 10 mg/m(2) was added in 3-weekly intervals. Treatment given on an outpatient basis, using portable pump systems, was repeated on day 57. Patients' characteristics were: male/female ratio 20/13; median age 57 (27-75) years; median WHO status 1 (0-2). 18 patients had a primary AGC, and 15 showed a relapsed AGC. Median follow-up was 11.8 months (range of those surviving: 2.7-11.8 months).. 32 patients were evaluable for response - complete remission 9.1% (n = 3), partial remission 45.5% (n = 15), no change 27.3% (n = 9), progressive disease 15.1% (n = 5). Median overall survival time was 10.2 months [95% confidence interval (CI): 8.7-11.6], and median progression-free survival time was 7.6 months (95% CI: 4.4-10.9). The worst toxicities (%) observed were (CTC-NCI 1/2/3): leukopenia 45.5/18.2/6.1, thrombocytopenia 33.3/9.1/6.1, vomitus 24.2/9.1/0, diarrhea 36.4/6.1/3.0, stomatitis 18.2/9.1/0, hand-foot syndrome 12.1/0/0. Two patients developed hemolytic-uremic syndrome (HUS).. High-dose 5-FU/FA/MMC is an effective and well-tolerated outpatient regimen for AGC (objective response rate 54.6%). It may serve as an alternative to cisplatin-containing regimens; however, it has to be considered that possibly HUS may occur.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil; Follow-Up Studies; Hemolytic-Uremic Syndrome; Humans; Infusion Pumps; Infusions, Intravenous; Leucovorin; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Neoplasm Staging; Palliative Care; Stomach Neoplasms; Survival Rate