Phase I trial of motexafin gadolinium in combination with docetaxel and cisplatin for the treatment of non-small cell lung cancer.
BACKGROUND
Motexafin gadolinium is a novel antineoplastic drug that disrupts cancer cell antioxidant systems, thus contributing to cellular death. In patients with lung cancer, motexafin gadolinium has been shown to increase the time to neurologic progression when given in combination with whole-brain radiotherapy in randomized phase III studies. Preclinical data suggest that this drug might also enhance the antineoplastic effects of chemotherapy.


METHODS
In this one-arm, open label, phase I, dose-escalation study, we administered docetaxel (75 mg/m2), cisplatin (75 mg/m2), and motexafin gadolinium every 3 weeks to patients with metastatic non-small cell lung cancer. Twenty-one patients were treated at one of four motexafin dose levels.


RESULTS
The maximal tolerated motexafin dose was 10 mg/kg on day 1 of a 3-week cycle. Dose-limiting toxicities consisted of febrile neutropenia, hypertension, myocardial ischemia, and pneumonitis/pulmonary infiltrates. Other common grade 3-4 adverse events across all cohorts that did not appear to be exacerbated by motexafin gadolinium included granulocytopenia, fatigue, dehydration, nausea, and vomiting. Two episodes of myocardial ischemia and one sudden death of unknown cause were observed. Response rates were partial response (10%), stable disease (60%), and disease progression (30%).


CONCLUSIONS
The regimen studied was tolerable and showed activity in patients with metastatic non-small cell lung cancer. The recommended doses for future phase II trials are motexafin gadolinium 10 mg/kg, docetaxel 75 mg/m2, and cisplatin 75 mg/m2 intravenously on day 1 every 3 weeks. Caution is advised in patients with a history of cardiovascular disease.
William
William N
WN
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Zinner
Ralph G
RG
Karp
Daniel D
DD
Oh
Yun W
YW
Glisson
Bonnie S
BS
Phan
See-Chun
SC
Stewart
David J
DJ
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D020714:Maximum Tolerated Dose; D008665:Metalloporphyrins / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
D008665:Metalloporphyrins; D043823:Taxoids; D000077143:Docetaxel; C437683:motexafin gadolinium; D002945:Cisplatin