A triplet chemotherapy with cisplatin, docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer: a phase I/II study.
OBJECTIVE
We conducted a phase I/II study of triplet chemotherapy consisting of cisplatin (CDDP), docetaxel (DCT) and gemcitabine (GEM) in patients with advanced non-small-cell lung cancer (NSCLC).


METHODS
Fifty-three untreated patients with stage IIIB or IV NSCLC were enrolled. All drugs were given on days 1 and 8. The doses of CDDP and DCT were fixed at 40 mg/m(2) and 30 mg/m(2), respectively. In the phase I portion, a dose escalation study of GEM with starting dose of 400 mg/m(2) was conducted and primary objective in the phase II portion was response rate.


RESULTS
The maximally tolerated dose (MTD) and recommended dose (RD) of GEM were determined as 800 mg/m(2) because grade 3 non-hematological toxicity (liver damage, diarrhea, and fatigue) developed in three of nine patients evaluated at that dose level. In pharmacokinetic analysis, C (max) and AUC of dFdC and dFdU were increased along with the dose escalation of GEM. However, no relationship between pharmacokinetic parameters and toxicity or response was observed. Objective response rate was 34% and median survival time was 11.7 months. Though major toxicity was myelosuppression, there were no life-threatening toxicities.


CONCLUSIONS
These results indicate that this triplet chemotherapy is feasible and effective in patients with advanced NSCLC.
Tabata
Masahiro
M
Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
Kozuki
Toshiyuki
T
Ueoka
Hiroshi
H
Kiura
Katsuyuki
K
Harita
Shingo
S
Tada
Atsuhiko
A
Shibayama
Takuo
T
Takigawa
Nagio
N
Yonei
Toshiro
T
Gemba
Kenichi
K
Segawa
Yoshihiko
Y
Kishino
Daizo
D
Tada
Shinya
S
Hiraki
Shunkichi
S
Tanimoto
Mitsune
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011247:Pregnancy; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D002945:Cisplatin; D000093542:Gemcitabine