Multicenter phase II trial of Motexafin gadolinium and pemetrexed for second-line treatment in patients with non-small cell lung cancer.

Abstract

BACKGROUND:

Motexafin gadolinium (MGd) disrupts redox-dependent pathways by inhibiting oxidative stress-related proteins leading to apoptosis. MGd selectively targets tumor cells, disrupting energy metabolism and repair mechanisms, rendering cells more prone to apoptosis. Preclinical studies with MGd and pemetrexed show significant tumor growth delay in lung cancer cell lines.

METHODS:

Patients with non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0 to 1, who had received one previous platinum containing regimen and normal organ function were treated with MGd 15 mg/kg and pemetrexed 500 mg/m q21days. Patients were allowed to receive more than one regimen if the initial treatment was in the adjuvant or curative setting and administered >12 months earlier. The primary end point was to demonstrate a 40% rate of 6-month progression free survival (PFS).

RESULTS:

Seventy-two patients (30 women, 42 men), performance status 0/1 (30/42), and a median age of 63 years were enrolled. Most patients (96%) were current or former smokers. All histologic types were represented (squamous/adenocarcinoma/other: 28%, 42%, 31%). Number of prior regimens: 1: 69%; 2: 26%, and >2: 4%. Median number of cycles administered was (range) 2 (1-12).

TOXICITY:

grade 3/4 neutropenia was noted in 8.3% with febrile neutropenia in 1.4%, thrombocytopenia in 8.3%, fatigue in 9.7%, and pneumonia in 11.1%. There were no complete responses, 8.1% had partial response, 56.5% had stable disease, and 35.5% had progressive disease as their best response. Twenty-three percent of patients were progression free at 6 months and the median PFS was 2.6 months with an overall survival of 8.1 months.

CONCLUSIONS:

The combination of MGd and pemetrexed was well tolerated with toxicity similar to that of pemetrexed alone. However, the study did not achieve its end point of 40% 6-month PFS. The response rate, PFS, and overall survival did not seem markedly different than prior phase II and phase III studies of pemetrexed alone. Consequently, there are no further plans for development of this combination.

• Authors: Martin J Edelman, Gregory Otterson, Joseph Leach, Thomas Malpass, Ravi Salgia, Dennie Jones, Tarak D Mody, Ramaswamy Govindan
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 6 Issue 4 Pg. 786-9 (Apr 2011) ISSN: 1556-1380 [Electronic] United States
• PMID: 21289521 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Glutamates
• Metalloporphyrins
• Pemetrexed
• Guanine
• motexafin gadolinium

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Female
• Follow-Up Studies
• Glutamates (administration & dosage)
• Guanine (administration & dosage, analogs & derivatives)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Metalloporphyrins (administration & dosage)
• Middle Aged
• Neoplasm Staging
• Pemetrexed
• Pilot Projects
• Prognosis
• Salvage Therapy
• Survival Rate