Camptosar(r), Cisplatin for Treatment of Advanced Non-small Cell Lung Cancer

Newswise — Results from the Phase III Four Arm Cooperative Study (FACS) of first-line treatment regimens for advanced non-small cell lung cancer (NSCLC) suggested that the combination of CAMPTOSAR® (irinotecan HCL for injection, CPT-11) and cisplatin should provide the best overall survival benefits and toxicity manageability among the four different regimens studied, including the current standard of treatment for NSCLC in the U.S., carboplatin plus paclitaxel. The results were presented today at the annual meeting of the American Society of Clinical Oncology (ASCO).

These data from the Japanese Cooperative Group indicated that platinum-based regimens containing paclitaxel, gemcitabine or vinorelbine were unable to demonstrate non-inferiority*, or were "inferior," on measures of median survival time, one-year survival rate, and response rate compared to the CAMPTOSAR plus cisplatin regimen. The CAMPTOSAR plus cisplatin regimen is a current standard of treatment for NSCLC in Japan.

"There remains a clear need for additional treatments for patients with this deadly disease," said Corey Langer, MD, Director, Thoracic and Head & Neck Medical Oncology at Fox Chase Cancer Center. "The response and survival results generated by the CAMPTOSAR/cisplatin regimen in this critical Japanese trial provide oncologists with a treatment option that can be used to treat patients with advanced NSCLC, without sacrificing quality of life."

One-year survival rates, median survival time and response rates for the CAMPTOSAR plus cisplatin arm were significantly above previous studies demonstrating 59.2%, 14.2% and 31% rates respectively. While the U.S. standard treatment regimen, carboplatin plus paclitaxel, showed 51%, 12.3% and 32.4% respective to the study endpoints. In addition, the carboplatin plus paclitaxel and gemcitabine plus cisplatin arms each showed higher, therapeutically-limiting toxicity profiles, including grade 3-4 neutropenia (reduction of white blood cells) and grade 3-4 thrombocytopenia (reduction of blood platelets). Study authors also note that the reference arm showed better than anticipated survival.

Preliminary data from a study being conducted by the Lung Cancer Solca Study Group, Athens, Greece, of combination therapy with CAMPTOSAR and paclitaxel in the first-line treatment of advanced NSCLC indicate that the combination is an effective therapy with acceptable toxicity. Among the first 38 evaluable patients, 18 patients (42.11%) have achieved partial remission and 16 patients (38%) have achieved stable disease. Additional studies are investigating combining CAMPTOSAR with non-platinum-based therapies as potential treatments for NSCLC.

"There is an increasing body of evidence that CAMPTOSAR is active in NSCLC," said S. Hariharan, MD, Medical Director at Pfizer Oncology. "The ability of CAMPTOSAR to be combined with platinum-based therapies as well as other agents to provide survival benefits suggests the flexibility and consistency of CAMPTOSAR."

About FACS (#7006)

The non-inferiority trial enrolled 602 patients at 44 centers across Japan. Results from 581 evaluable patients were presented. Eligible patients with stage IIIb (malignant pleural effusion and/or metastasis in the same lobe)/IV were randomly assigned to one of three investigational arms or to the CAMPTOSAR-based reference arm. CAMPTOSAR and cisplatin (IP) was compared to three different investigational platinum-based regimens including, carboplatin plus paclitaxel (TC), gemcitabine plus cisplatin (GP), and vinorelbine plus cisplatin (NP) in the first-line treatment of patients with stage IIIb/IV NSCLC. Endpoints included one-year survival rate, median survival time, and response rate.

Overall results from the four arms showed one-year survival rates (TC: 51.0%; GP: 59.6%; NP: 48.3%; IP: 59.2), median survival time (TC: 12.3 months; GP: 14.8 months; NP: 11.4 months; IP: 14.2 months), and response rates (TC: 32.4%; GP: 30.1%; NP: 33.1%; IP: 31.0%), in the investigational arms were insufficient to demonstrate non-inferiority over the reference arm.

Patient toxicities were evaluated for grade 3-4 neutropenia (TC: 87.8%; GP: 62.9%; NP: 88.4%; IP: 83.7%), grade 3-4 thrombocytopenia (TC: 10.8%; GP: 35.1%; NP: 0.7%; IP: 5.4%), grade 2-4 nausea (TC: 24.3%; GP: 57.6%; NP: 47.3%; IP: 60.5%), grade 2-4 diarrhea (TC: 4.7%; GP: 5.3%; NP: 8.2%; IP: 48.3%), grade 2-4 sensory neuropathy (TC: 23.0; GP: 0.0%; NP: 0.0%; IP: 1.4%).

About the paclitaxel/ CAMPTOSAR Study (#7127)

The ongoing study, being conducted by the Lung Cancer Solca Study Group, Athens, Greece, is investigating the potential of combination therapy with paclitaxel and CAMPTOSAR in the first-line treatment of advanced NSCLC. As of December 5, 2003, 51 patients with previously untreated grade IIIb/IV NSCLC have been enrolled in the study.

All study subjects will receive 200mg/m2 CAMPTOSAR via a 90-minute infusion and 135 mg/m2 paclitaxel via a 3-hour infusion on day one of each two-week cycle and be evaluated via CT-Scan following the 4th or 5th treatment cycle for disease progression. Study protocol calls for patients to receive 9 cycles of therapy. Results from 33 evaluable patients who have completed an average of 4.92 cycles of therapy show the regimen to have a 42.11% response rate with acceptable toxicity. Results indicated partial remission in 18 patients (42.11%), stable disease in 16 (38%) patients, and disease progression in 4 patients (10.53%). Survival data from this study is not yet available.

The most commonly experienced adverse events included grade 1-2 myelotoxicity, and grade I neurotoxicity. Grade 3-4 adverse events included: 4 patients (10.53%) who experienced grade 3-4 myelotoxicity and 5 patients (13.16%) who experienced grade III diarrhea.

About CAMPTOSAR® (irinotecan hydrochloride injection)

CAMPTOSAR® is approved in combination with 5-fluorouracil/leucovorin (5-FU/LV) as initial, or first-line, therapy for the treatment of advanced (metastatic) colorectal cancer. The combination shown to increase survival in multiple studies has demonstrated consistent success in first-line treatment in objective tumor response rates and time to tumor progression. CAMPTOSAR is also a central component of combination therapy playing a primary role in the studies that supported the FDA approvals of molecular targeted agents, Avastin™ and Erbitux™.

CAMPTOSAR is associated with neutropenia and both early and late forms of diarrhea, which can be life threatening if not managed properly.

Full prescribing and safety information, including black box warning, can be found at http://www.pfizeroncology.com/camptosar

About Pfizer Oncology

Pfizer Oncology is committed to advancing the scientific understanding of cancer and to bringing new medicines to millions of cancer patients. Oncology is a research priority for Pfizer, with over 12 percent of the company's research and development investment devoted to discovering and developing innovative therapies for treating breast, colorectal and other cancers.

Pfizer Inc discovers, develops, manufactures and markets leading prescription medicines for humans and animals and many of the world's best-known consumer brands.

* A statistical analysis of existing test data where the sole purpose is to determine if the one therapy is clinically equivalent to the second therapy.