Phase I study of escalating doses of oxaliplatin in combination with fixed dose gemcitabine in patients with non-small cell lung cancer.
OBJECTIVE
Oxaliplatin (OHP) is a new platinum antineoplastic, while gemcitabine (GEM) is one of the most active drugs against non-small cell carcinoma (NSCLC). The OHP/GEM combination is interesting because the drugs have different mechanisms of action and toxicity profiles. The primary endpoint of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of OHP/GEM combination in non-small cell carcinoma of the lung.


METHODS
Patients with relapsed NSCLC were treated with fixed dose i.v. GEM (1250 mg/m2) on days 1 and 8; followed on day 1 by i.v. OHP over 3 h, starting from 70 mg/m2 with 20 mg/m2 increments, up to 130 mg/m2. We enrolled 19 patients with eastern cooperative oncology group (ECOG) status 0/1=13/6; male/female=13/6. All had received first-line and four second-line chemotherapy.


RESULTS
Four patients dropped out. At dose level 2, one patient died of pulmonary embolism; at level 3, two patients died of disease progression. One patient at level 3, refused to continue treatment after allergic reaction (high fever episode) during infusion of third cycle. Fifteen patients were evaluable for toxicity and response. According to a priori statistical considerations, three patients in each of the first three treatment levels and six in the last level were evaluable. No G3-4 toxicity was observed at levels 1 and 2. G3 neutropenia and anemia occurred in 8% of cycles at level 3. Six patients entered level 4 (OHP 130 mg/m2) with 22 courses delivered: G3-4 neutropenia occurred in 9%, G1-2 thrombocytopenia in 18%; other toxicities were mainly limited to G1-2 flu-like syndrome in about one third of patients and G1-2 nausea and vomiting in 5% of courses. There was no myelo-DLT at the highest dose level. There was no neurotoxicity at any level. Treatment was delayed in 12% and dose reduced in 26% of courses. There were 2/15 PR.


CONCLUSIONS
MTD was not reached. OHP and GEM can probably be administered safely at 130 and 1250 mg/m2, respectively, as first-line therapy. The schedule is being used in a phase II trial.
Bidoli
Paolo
P
Medical Oncology Unit B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, Milano 20133, Italy.
Stani
Simonetta C
SC
Mariani
Luigi
L
De Candis
Daniela
D
Cortinovis
Diego
D
Aglione
Stefania
S
Zilembo
Nicoletta
N
Toffolatti
Luisa
L
Formisano
Barbara
B
Bajetta
Emilio
E
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D013921:Thrombocytopenia / Q000139:chemically induced; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000093542:Gemcitabine