A combination phase I study of weekly paclitaxel and doxifluridine in advanced gastric cancer patients.
BACKGROUND
Preclinical studies have shown that paclitaxel and doxifluridine can act synergistically without overlapping toxicity for the treatment of advanced gastric cancer. The objectives of this study were to determine the maximum tolerated dose (MTD), the dose-limiting toxicity and the recommended Phase II dose for this drug combination.


METHODS
Patients with histologically confirmed gastric cancer were eligible for the study. The paclitaxel dose (days 1, 8, 15) was augmented with a fixed dose of for treatments (1-3). doxifluridine (533 mg/m2, 5 days/week) on a 28-day cycle.


RESULTS
Eighteen patients were enrolled. The MTD was not reached until the highest dose level. One patient had Grade 3 myelosuppression. The responses of the 13 suitable patients included 1 complete response and 5 partial responses.


CONCLUSIONS
Although the MTD level could not be definitively which is a established, upon consideration of the lengthy administration time and the effectiveness, the recommended Phase II dose of paclitaxel was concluded to be 80 mg/m2 in combination with doxifluridine at 533 mg/m2.
Takeyoshi
Izumi
I
Second Department of Surgery, Gunma University, Faculty of Medicine, Japan. takeyosi@showa.gunma-u.ac.jp
Makita
Fujio
F
Tanahashi
Yoshifumi
Y
Yokomori
Tadahiro
T
Iwazaki
Shigeru
S
Kawashima
Yoshiyuki
Y
Iwanami
Kotaro
K
Yamada
Tatsuya
T
Kawate
Susumu
S
Hamada
Kunihiro
K
Sunose
Yutaka
Y
Yoshida
Miho
M
Horiguchi
Jun
J
Iesato
Hiroshi
H
Kobayashi
Mitsunobu
M
Morishita
Yasuo
Y
D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005467:Floxuridine / Q000008:administration & dosage* / Q000009:adverse effects; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014839:Vomiting / Q000139:chemically induced
D005467:Floxuridine; D017239:Paclitaxel; C025034:doxifluridine