Study With Mitomycin c/5-FU/FA in Pretreated Gastrointestinal Cancer Patients With Metastases (>= Second-line Treatment)

Open, Multi-center Phase I/II Trial With Mitomycin C in Combination With 5-Fluorouracil and Folinic Acid in Pretreated Patients With Metastatic Gastrointestinal Cancer

The aim of this study was to define the maximum tolerated dose (MTD) of bolus mitomycin C (MMC) in combination with 24 h-continuous infusion of 5-fluorouracil (FU) plus folinic acid, and to assess the toxicity and activity in patients with previously treated colorectal and gastric cancer. Escalating doses of MMC starting from 6 mg m(-2) in 2 mg m(-2)-steps to a maximum of 10 mg m(-2) were applied on days 1 and 22, given to fixed doses of 5-FU (2.600 mg m(-2)) as 24 h infusion and folinic acid 500 mg m(-2) prior to 5-FU weekly for 6 weeks

Inclusion Criteria:

Phase 1 (dose escalation)

• patients with histological proven gastrointestinal neoplasms, without standard therapy option
• measurable or evaluable disease
• >= second-line therapy (metastasized stage) Phase 2 (efficacy)
• patients with proven colorectal neoplasms
• measurable disease, metastasized
• previous chemotherapy with 5-FU/FA ("AIO-regimen")
• age between 18 and 75 years, both male and female
• life expectancy > 3 months
• WHO-performance status <= 2
• adequate bone marrow function: hemoglobin >= 10 mg/dl, neutrophils >= 2.0 * 1000000000/l, thrombocytes >= 150 * 1000000000/l
• adequate renal and liver function: bilirubin <= 1.25 * ULN(<= 1.5 ULN * by liver metastases), creatinine <= 1.25 * ULN, ASAT and ALAT <= 3 * ULN (<= 5* ULN by liver metastases; AP <= 3* ULN
• written informed consent prior to inclusion into the study

Exclusion Criteria:

• pretreated with mitomycin c
• contraindication concerning 5-FU (e.g. anxiety, myocardial infarction within last 6 months, significant toxicities during previous therapy with 5-FU
• florid infections
• ileus or subileus, morbus crohn or colitis, ulcerative
• actual chronic diarrhea
• other uncontrolled severe concurrent disease excluding cytotoxic intervention
• second malignancy except basal cell carcinoma or cervical carcinoma in situ
• known cns metastases or carcinomatous leptomeningitis
• pregnancy or lactation period
• no effective contraception
• concomitant treatment with another antineoplastic agents
• participation in another clinical trial within the last 4 weeks
• patients being unwilling or unable to undergo trial specific procedures