O-151 Phase II study of anatumomab mafenatox (ABR-214936) in advanced NSCLC: Results of a multi-institutinal open label repeat dose trial with patient-specific dose escalation

Purpose: To further investigate the efficacy and safety of temozolomide plus thalidomide in patients with metastatic melanoma without brain metastases. Patients and Methods: Patients with histologically confirmed advanced-stage metastatic melanoma were enrolled in an open-label, phase II study. The primary end point was response rate. Patients received temozolomide (75 mg/m2/d × 6 weeks with a 2-week rest between cycles) plus concomitant thalidomide (200 mg/d with dose escalation to 400 mg/d for patients < 70 years old, or 100 mg/d with dose escalation to 250 mg/d for patients ≥ 70 years old). Treatment was continued until unacceptable toxicity or disease progression occurred. Results: Thirty-eight patients (median age, 62 years) with stage IV (three patients with M1a, eight with M1b, and 26 with M1c) or stage IIIc (one patient) melanoma and a median of four metastatic sites were enrolled, and received a median of two cycles of therapy. Twelve patients (32%) had an objective tumor response, including one with an ongoing complete response of 25+ months’ duration and 11 with partial responses. Five patients achieving partial response with a more than 90% reduction of disease were converted to a complete response with surgery. Treatment was generally well tolerated. Median survival was 9.5 months (95% confidence interval, 6.05 to 19.38 months), with a median follow-up among survivors of 24.3 months. Conclusion: The combination of temozolomide plus thalidomide seems to be a promising and well-tolerated oral regimen for metastatic melanoma that merits further study.

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Activity of patupilone for the treatment of recurrent or progressive brain metastases in patients (pts) with non-small cell lung cancer (NSCLC): An open-label, multicenter, phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18058 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18058-18058 ◽

Cited By ~ 4

Author(s):

L. Abrey ◽

P. Y. Wen ◽

R. Govindan ◽

H. J. Reimers ◽

J. R. Rigas ◽

...

Keyword(s):

Brain Metastases ◽

Disease Progression ◽

Phase Ii ◽

Advanced Nsclc ◽

Phase Ii Study ◽

Study Drug ◽

Open Label ◽

Antitumor Effects ◽

Multicenter Phase ◽

Grade 3

18058 Background: Advances in systemic chemotherapy have improved overall survival for patients with advanced NSCLC; unfortunately, CNS metastasis is common and limits survival benefits with current therapies. Unlike taxanes, preclinical findings suggest that the novel epothilone, patupilone, crosses the blood-brain barrier in 3 animal species and also has antitumor effects in brain tumor models. Results of an ongoing phase I/II study of patupilone as second-line therapy in pts with NSCLC are encouraging. The present study is evaluating the efficacy of patupilone in pts with brain metastases from NSCLC who have failed or recurred after previous chemotherapy, surgery, and/or radiation to the brain. Methods: This open-label, single-arm, multicenter, phase II study has a 2-stage design (25 pts per stage). Eligible pts have histologically confirmed NSCLC and = 1 recurrent, bidimensionally measurable intracranial lesion = 2 cm. Patupilone was administered IV at 10 mg/m2 as a single 20-min IV infusion every 3 weeks until disease progression, satisfactory response, or unacceptable toxicity. The primary multinomial endpoint was a combination of early progression (disease progression or death before cycle 1, day 21) and response rate (alive without progression at cycle 4, day 1). Results: An interim analysis of 13 pts with a median age of 62 years (range, 40–67 years) is reported. The most common adverse events (AEs) related to study drug were NCI CTC grade 1/2 diarrhea in 7 (54%) pts, nausea in 3 (23%), and fatigue in 2 (15%). Only 2 serious AEs (grade 4 colitis and grade 3 diarrhea) and 2 additional grade 3 AEs (diarrhea, neutropenia) were reported in 1 pt each. Three (23%) pts experienced early disease progression. Five (38%) pts responded, receiving a median 10 cycles (range, 5 to 12 cycles) and were alive without progression on cycle 4, day 1. Conclusions: Patupilone has activity in patients with CNS metastases from advanced NSCLC and is well tolerated. Additional investigation of patupilone as a treatment for brain metastases from NSCLC is warranted. [Table: see text]

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