Phase I trial of gemcitabine and CPT-11 given weekly for four weeks every six weeks.
BACKGROUND
Our previous studies have shown that the in vitro cytotoxicity of gemcitabine and SN-38, the active metabolite of irinotecan (CPT-11), is synergistic in human tumor cell lines.


METHODS
Twenty-four patients with solid tumors, refractory to standard chemotherapy or for whom no effective therapy existed (age range 31-74; 7 female, 17 male; ECOG PS 0 = 12, 1 = 11, 2 = 1), received gemcitabine and CPT-11 weekly for four weeks out of every six weeks. Fifty courses of treatment (median 2, range 1-8) were given through five dose levels of gemcitabine/CPT-11 (600/75, 800/75, 800/100, 1000/100, 1000/125 mg/m2).


RESULTS
Grade 3 and 4 neutropenia occurred in eight and two patients, respectively. Grade 3 and 4 thrombocytopenia occurred in one and three patients, respectively. Hematologic toxicity resulted in > or = 2 missed doses of treatment in two out of six patients and was therefore dose limiting at gemcitabine 1000 mg/m2 and CPT-11 125 mg/m2. Grade 3 and 4 diarrhea occurred in two and one patients, respectively. Other moderate non-hematologic toxicities included alopecia, anorexia, fatigue, nausea, vomiting, and weight loss.


CONCLUSIONS
The maximum tolerated dose for this study recommended for phase II testing is gemcitabine 1000 mg/m2 and CPT-11 100 mg/m2. A partial response was seen in transitional cell carcinoma.
Alberts
S R
SR
Division of Medical Oncology and Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
Erlichman
C
C
Sloan
J
J
Okuno
S H
SH
Burch
P A
PA
Rubin
J
J
Pitot
H C
HC
Goldberg
R M
RM
Adjei
A A
AA
Atherton
P J
PJ
Kaufmann
S H
SH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D000093542:Gemcitabine
D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine