一些肺癌资料

Susan

Below is an article about three promising drugs for NSCLC.

http://www.medscape.com/viewarticle/540166

July 6, 2006 (Atlanta) — Two drugs recently approved for use in renal cell carcinoma, sorafenib (Nexavar, Bayer) and sunitinib (Sutent, Pfizer), have shown promising activity in uncontrolled phase 2 trials in patients with advanced non–small cell lung cancer (NSCLC), researchers reported at the recent 42nd meeting of the American Society of Clinical Oncology. A third drug, the investigational agent ZD6474 (Zactima, AstraZeneca), showed a significant advantage over the marketed drug gefitinib (Iressa, AstraZeneca) in a double-blind, randomized phase 2 trial presented at the same session.

All 3 drugs are administered orally, and all are kinase inhibitors, although they differ with respect to the signaling pathways that they inhibit. "They all have slightly different target specificities and toxicities," said Roy Herbst, MD, chief of thoracic medical oncology at the University of Texas MD Anderson Cancer Center in Houston. He was discussant for these presentations at the meeting.

"All 3 drugs clearly have some activity in NSCLC, but how they will compare with standard chemotherapy and/or be combined will be the key question," Dr. Herbst told Medscape.

Sunitinib Shows Provocative Single-Agent Activity

Sunitinib is approved for use in gastrointestinal stromal tumors as well as renal cell carcinoma and is being investigated in various other tumor types. At the meeting, lead author Mark Socinski, MD, from the Lineberger Comprehensive Cancer Center, University of North Carolina, Durham, presented results from the first trial of the drug in lung cancer, saying the drug exhibited "provocative single-agent activity in previously treated patients with recurrent and advanced NSCLC," with a level of activity similar to agents that are already approved for this indication.

The trial was conducted in 63 patients, who received 50-mg sunitinib daily for 4 weeks, followed by 2 weeks off treatment. Patients continued on this regimen until their disease progressed.

So far, 6 confirmed partial responses (9.5%) have been observed, and stable disease has been observed in an additional 26 patients (41%), Dr. Socinski reported.

The drug was well tolerated, and most side effects were mild to moderate, the researchers said in a press release. Serious side effects were less common and included severe fatigue (19%), shortness of breath (13%), asthenia 9.5%, and nausea/vomiting (7%). Three patients died, 2 from pulmonary hemorrhage and 1 from cerebral hemorrhage.

"Our findings suggest that sunitinib may have a place in the treatment of lung cancer, alone or in combination with other agents," Dr. Socinski concluded. Further trials are ongoing, both with sunitinib alone and in combination with other agents, including one exploring the use of sunitinib with erlotinib (Tarceva, Genentech).

Promising Efficacy Seen With Sorafenib

Sorafenib was also tested as a single agent in a phase 2 trial reported by Ulrich Gatzemeier, MD, from the Hospital Grosshandsdorf, Hamburg, Germany. The drug showed "promising efficacy in patients with advanced, progressive NSCLC, with approximately 60% of patients achieving disease stabilization," he told the meeting.

This trial enrolled 54 patients, of whom 52 received sorafenib (400 mg twice daily), and 51 were evaluable for efficacy. Of these 51 patients, 30 (59%) had stable disease, with a median progression-free survival of 23.7 weeks. Although there were no confirmed partial responses, tumor shrinkage was observed in 15 patients (29%), and 4 patients showed shrinkage of 30% or more of their tumor. Overall, the 51 evaluable patients had a median overall survival of 29.3 weeks.

Sorafenib was generally well tolerated, Dr. Gatzemeier commented. The most frequent drug-related adverse effects were diarrhea (40% of patients), hand-foot skin (HFS) reaction (37%), fatigue (27%), and nausea (25%); the more serious reactions included HFS reaction in 10% and hypertension in 4% of patients. Three patients discontinued because of adverse effects (HFS reaction, elevated lipase levels, and myocardial infarction).

Investigational Drug ZD6474

The third drug, ZD6474, is not available yet; it is in phase 3 trials in NSCLC and in phase 2 trials in small cell lung cancer and thyroid cancer. It acts by inhibiting vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and rearranged-during-transfection (RET) receptor tyrosine kinase activity. In the trial reported by Ronald B. Natale, MD, from the Cedars-Sinai Outpatient Cancer Center, Los Angeles, California, it was pitted against gefitinib, which inhibits epidermal growth factor receptor (EGFR) tyrosine kinase. Gefitinib is marketed for NSCLC, but its use is limited by new labeling the FDA announced last year. This move came after clinical trials showed that gefitinib did not improve survival in this patient population, whereas other drugs such as erlotinib and docetaxel (Taxotere, Sanofi Aventis) have been shown to prolong survival.

The trial was conducted in 168 patients with NSCLC who had failed platinum-based chemotherapy, and in the first part patients took either ZD6474 (300 mg) or gefitinib (250 mg) until disease progression or evidence of toxicity.

Patients taking the investigational drug had a significantly longer progression-free survival, 11 weeks for ZD6474 vs 8.1 weeks for gefitinib (hazard ratio, 0.69; P = .025). This was the primary efficacy objective of the trial, and the fact that the new drug met this objective supports further confirmatory trials of the product in NSCLC, Dr. Natale commented. In addition, disease control for longer than 8 weeks was achieved in 37 of 83 patients (45%) taking ZD6474 compared with 29 of 85 (34%) receiving gefitinib.

In the second part of the trial, after a washout period of 4 weeks, more of the patients (16 of 37) who switched to ZD6474 from gefitinib had disease control for longer than 8 weeks, compared with the proportion (7 of 29) who had switched from the new drug to gefitinib. However, overall survival was not significantly different in the 2 groups (median 6.1 months in the ZD6474 group vs 7.4 months in the gefitinib group).

The adverse-event profile of ZD6474 was similar to that seen in previous trials of the drug, Dr. Natale told the meeting, with diarrhea (grade 3/4) in 8.4% of patients, rash (grade 3/4) in 4.8%, and asymptomatic QTc prolongation (all grade 1) in 20.5% of patients.

ASCO 42nd Annual Meeting: Abstracts 7000, 7001, and 7002. Presented June 4, 2006.

jimmy112199

Hello, Susan,  I read your post about HKI-272, Do you know where we could enroll this kind of clinical trial, I am in NYC, my father has lung cance for two years.

thank you