The aim of this study was to evaluate the toxicity and efficacy of
combination chemotherapy with weekly 24-h continuous infusion of
5-fluorouracil (5-FU)/
folinic acid, weekly
paclitaxel and 3-weekly
cisplatin in patients with unresectable, locally advanced or metastatic gastric
adenocarcinoma. Between November 1999 and November 2001, 29
chemotherapy-naive patients (13 male and 16 female) with a median age of 56 years (range 22-72) were consecutively enrolled at three centers.
5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by
folinic acid 500 mg/m2 as a 2-h infusion.
Paclitaxel 80 mg/m2 was administered as a 1-h infusion weekly and
cisplatin 50 mg/m2 as 1-h infusion on days 8 and 29. Six weeks of
therapy (days 1, 8, 15, 22, 29 and 36) followed by 1 week of rest was considered one cycle. A median of 3 cycles (range 1-5) was administered to 29 patients with a total of 73 cycles applied. All patients were assessable for toxicity and survival, 28 patients were assessable for response (one patient received less than one complete cycle and could not be evaluated for response). Four patients (14%) obtained a complete response and 10 patients (34%) a partial response (overall response rate 48%, 95% CI 29-68%). Seven patients (24%) had stable disease. Seven patients (24%) had progressive disease during or within 4 weeks
after treatment. The median progression-free and overall survival times were 8 months (range 1-23) and 11 months (range 1-23), respectively. Overall toxicity was acceptable. Hematological toxicity was favorable with only one patient (3%) experiencing WHO grade 3/4
leukocytopenia and one patient (3%) WHO grade 3/4
anemia. Non-hematologic WHO grade 3/4 toxicities included
alopecia in 19 (66%),
nausea/
vomiting in six (21%),
diarrhea in six (21%), neurotoxicity grade 3 in three (10%) and
infection in three (10%) patients. A total of 42 applications (10%) (range 0-5) had to be postponed and
dose reductions of at least one
drug was necessary in 37% of applications. In three patients (10%) treatment was stopped because of toxicity. All patients were treated on an outpatient basis. Thus, the combination of weekly
paclitaxel, cisplatin and continuously infused 5-FU/
folinic acid appears to be a highly active regimen for the treatment of patients with advanced
gastric cancer. Compared with our previous experience with the same combination of drugs but using
paclitaxel at 175 mg/m2 given every 3 weeks, the protocol with weekly application of
paclitaxel 80 mg/m2 shows a reduced incidence of hematologic toxicity, particularly
leukopenia. Other organ toxicities apart from a slightly higher incidence of
peripheral neuropathy were comparable between the two treatment protocols. Efficacy with a response rate of 50% was well preserved by this weekly regimen.