title: Phase II study of continuous 120 h infusion of mitomycin C as salvage chemotherapy in patients with progressive or rapidly recurrent colorectal cancer.
abstract: We evaluated the therapeutic activity and safety of continuously infused mitomycin C in patients with metastatic colorectal cancer who had recurred (less than 3 months) or progressed following first- or second-line 5-fluorouracil-based chemotherapy. Treatment consisted of mitomycin C 20 mg/m2 i.v. given over 120 h (5 days) followed by a 3 week rest period. Fifty-two consecutively enrolled patients were assessable for toxicity and 49 for response evaluation (three patients evaluable but not measurable), completing at least one full course of chemotherapy. Previous chemotherapy regimens consisted of bolus 5-fluorouracil/folinic acid (5-FU/FA) (Machover) n=26 (50%) or continuous (24 h) 5-FU+/-FA+/-interferon n=26 (50%). Forty-two percent of patients had received one previous chemotherapy regimen and 58% more than one. One partial remission (2%) lasting 7 months and 11 disease stabilizations (23%) with a median duration of 3.2 months (range 1-8) were achieved in 49 patients. Median survival time since start of mitomycin C was 4.7 months (1.2-28.1) resulting in a 6 month survival rate of 36%. The progression-free interval was 10 weeks (range 4-36). Delayed and cumulative thrombo- and leukocytopenia (WHO grade III/IV) were observed in 19 and 6%, and anemia in 2% of patients. WHO grade I/IV mucositis, diarrhea and fever/infection occurred each in 6% of patients. Treatment delays and dose reductions were necessary in 11 (21%) and 21 (40%) patients, respectively. In three cases treatment was stopped due to cumulative thrombocytopenia (6%). Continuous infusion of single-agent mitomycin C displays modest activity in heavily pretreated 5-FU refractory colorectal cancer patients combined with a low toxicity level.
authors.affiliation: Department of Hematology, UKL-University Medical Center II, Eberhard-Karls-University, Tübingen, Germany.
authors.forename: J T
authors.initials: JT
authors.lastname: Hartmann
authors.forename: A
authors.initials: A
authors.lastname: Harstrick
authors.forename: T
authors.initials: T
authors.lastname: Daikeler
authors.forename: C
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: C
authors.initials: C
authors.lastname: Müller
authors.forename: S
authors.initials: S
authors.lastname: Seeber
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000009:adverse effects / Q000627:therapeutic use*; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D016879:Salvage Therapy; D013280:Stomatitis / Q000139:chemically induced; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D016685:Mitomycin