High incidence of pulmonary toxicity of weekly docetaxel and gemcitabine in patients with non-small cell lung cancer: results of a dose-finding study.
OBJECTIVE
To determine the maximum tolerated doses (MTD) and the dose-limiting toxicities (DLTs) of the weekly administration of docetaxel and gemcitabine as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC).


METHODS
Chemotherapy-naïve patients with histologically or cytologically confirmed unresectable stage III(B) or IV NSCLC were enrolled onto the study. Escalated doses of gemcitabine (starting dose 700 mg/m(2) per week) and docetaxel (starting dose 30 mg/m(2) per week) were given on a weekly basis for three consecutive weeks in cycles of 4 weeks.


RESULTS
Twenty-six patients received a total of 94 chemotherapy cycles. At the doses of docetaxel 40 mg/m(2) per week and gemcitabine 1000 mg/m(2) per week, the MTD had not yet been reached. However, the study was prematurely closed because of a high incidence of severe pulmonary adverse events. Six (23%) patients developed fever and pulmonary dysfunction (severe dyspnea, hypoxia in association with diffuse interstitial pneumonitis), which was fatal in two of them. No risk factors were identified contributing to these pulmonary adverse events; four patients had a low absolute number of peripheral blood CD4+ lymphocytes. Grade 3/4 neutropenia occurred in five (19%) patients and grade 3/4 anemia in two (8%).


CONCLUSIONS
The weekly administration of gemcitabine and docetaxel in patients with advanced NSCLC is associated with a high incidence of severe pulmonary toxicity, which does not seem to be dose-related. The regimen cannot be used outside a clinical protocol.
Kouroussis
Charalambos
C
Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, Heraklion 71110, Crete, Greece. georgsec@med.uoc.gr
Mavroudis
Dimitris
D
Kakolyris
Stylianos
S
Voloudaki
Argyro
A
Kalbakis
Konstantinos
K
Souglakos
John
J
Agelaki
Sophia
S
Malas
Konstantinos
K
Bozionelou
Vassiliki
V
Georgoulias
Vassilis
V
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008171:Lung Diseases / Q000139:chemically induced* / Q000453:epidemiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D043823:Taxoids / Q000009:adverse effects*; D000093542:Gemcitabine
D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine