Pilot study of low-dose, divided maximum tolerated dose of CPT-11 in 21 consecutive patients with metastatic colorectal or gastric cancer.
OBJECTIVE
We devised a new treatment regimen, delivering a frequent low dose of CPT-11, calculated by dividing the maximum tolerated dose (MTD) to reduce its toxicity without impairing its efficacy.


METHODS
CPI-11, 25 mg/m2, determined by dividing the MTD dose per month by 12, was given on days 1, 2, and 3 of every week, to 21 consecutive patients; 12 with metastatic colon cancer and 9 with metastatic gastric cancers.


RESULTS
The total delivered dose of CPI-11 per patient was more than 1,000 mg in 17 (80.1%) of the 21 patients. Grade 3 marrow depression developed in 3 (14.3%) patients, and although nausea, vomiting, alopecia, and diarrhea developed in some patients, these side effects were all categorized as grade 2 or milder. The antitumor effect was evaluated in 18 patients with measurable lesions, who had received CPI-11 according to our regimen for at least 3 weeks. Of these 18 patients, 10, 7, and 1, respectively, had a found to have partial response, no change, or progression of disease, demonstrating a 55.6% efficacy rate [colon 6/10 (60.0%) and stomach 4/8 (50.0%)]. Moreover, time to progression (TTP) was greater than 90 days in 12 (75.0%) of these 18 patients.


CONCLUSIONS
These results show that our low-dose, divided MTD of CPI-11 regimen is a promising method of reducing toxicity and strengthening the antitumor effect, justifying further large-scale comparative clinical studies to verify this potential.
Takahashi
Yutaka
Y
Department of Surgical Oncology, Cancer Research Institute, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8641, Japan.
Kitakata
Hidekazu
H
Yamashita
Kaname
K
Yasumoto
Kazuo
K
Omote
Kazuhiko
K
Minamoto
Toshinari
T
Mai
Masayoshi
M
D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010865:Pilot Projects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin