Nexavar in non-small cell lung cancer – pro

M Levin, MD — Thu, 23 Aug 2012 17:21:05 +0000

Nexavar is an orally active, multi-kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced renal cell carcinoma. Nexavar has wide anti-tumor effects and has been tested in a variety of other cancers, including prostate and melanoma.In a pilot study, 6 patients with recurrent NSCLC were treated with single agent Nexavar®. This study demonstrated single agent activity with partial responses in two patients and stable disease in two others. This led to a larger study involving 52 patients with relapsed NSCLC treated with single agent Nexavar. In this study there were no partial or complete remissions, but 59% had stable disease. The median progression-free survival was 2.7 months and the overall survival was 205 days. There were no grade IV toxicities. 8% of patients in this study had bleeding. Three patients in this study had Nexavar discontinued due to hand-foot syndrome, elevated lipase and myocardial infarction. A quality of life study concluded that Nexavar did not adversely impact patient-reported outcomes in function and symptom response during treatment.

The results of a phase I clinical trial evaluated the combination of Nexavar and Iressa® (gefitinib) for the treatment of 32 patients with refractory or recurrent NSCLC were presented at the 2005 ASCO meeting. It was concluded that Nexavar and Iressa was a safe combination for treating patients with NSCLC.

In another phase I/II clinical trial, Nexavar was combined with Taxol® (paclitaxel) and Paraplatin® (carboplatin) for treatment of 15 patients with advanced progressive NSCLC. The partial response rate was 29% and 50% had stable disease for a disease control rate of 79%. The median duration of response was 25 weeks and progression-free survival was 7.5 months. There appeared to be no increase in toxicity from adding Nexavar to Taxol and Paraplatin in this study.

Recently, however, Nexavar was dropped from an ongoing trial. Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals have stopped a late stage trial of their cancer drug Nexavar (sorafenib) in patients with nonsmall-cell lung cancer (NSCLC), because it was not showing the hoped for increase in survival. The ESCAPE study was a multicentre, randomized, double-blind, placebo controlled phase 3 trial involving more than 900 NSCLC patients at over 140 clinics in North and South America, Europe and Asia.
Following a planned interim analysis, the trial’s independent data monitoring committee (DMC) concluded that the drug was not going to meet the trial’s main goal of improving overall survival.

In conclusion, although the discontinuation of Nexavar in a phase III trial throws a shadow upon its future role in lung cancer, there are several suppooting phase II trials and it should be considered supported by medical literature.

Liu B, Barrett P, Choyke K, et al. A phase II study of BAY 43-9006 (sorafenib) in patients with relapsed non-small cell lung cancer (NCLC). Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I, Vol 24, No 18S (June Supplement), 2006:abstract 17119.

Gatzemeier U, Blumenschein F, Fosella R, et al. Phase II trial of single-agent sorafenib in patients with advanced non-small cell lung carcinoma. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I, Vol 24, No 18S (June Supplement), 2006:abstract 7002.

Gondek K, Dhanda R, Simantov R, et al. Health-related quality of life measures in advanced non-small cell lung cancer patients receiving sorafenib. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I, Vol 24, No 18S (June Supplement), 2006:abstract 17085.

Adjei AA, Mandrekar S, Marks S, et al. A phase I study of BAY 43-9006 and gefitinib in patients with refractory or recurrent non-small cell-lung cancer (NSCLC). Journal of Clinical Oncology 2005 ASCO Annual Meeting Proceedings. Vol 23, No. 16S, Part I of II (June 1 Supplement), 2005:abstract 3067.

SAMSA – A New Drug for Low Sodium – pro

M Levin, MD — Fri, 10 Aug 2012 00:29:41 +0000

SAMSCA is indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure, cirrhosis, and Syndrome of Inappropriate Antidiuretic Hormone (SIADH). Thiis condtion occurrs with lung cancer and less commonly other cancer or in associaitons with certain chemotherapy drugs that are used to treat cancer, such as cisplatin.

SAMSCA should be initiated and re-initiated in patients only in a hospital where serum sodium can be monitored closely. This allows observing for side efects and to titrate to an appropraite dose. The FDA aproved Prescribing information says: “The usual starting dose for SAMSCA is 15 mg administered once daily without regard to meals. Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium. ”

Cavalcante JL, Khan S, Gheorghiade M EVEREST study: Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan. Expert Review of Cardiovascular Therapy 2008 Nov;6(10):1331-8

Madias NE Effects of tolvaptan, an oral vasopressin V2 receptor antagonist, in hyponatremia. American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 2007 Aug;50(2):184-7

Miyazaki T, Fujiki H, Yamamura Y, Nakamura S, Mori T Tolvaptan, an orally active vasopressin V(2)-receptor antagonist – pharmacology and clinical trials. Cardiovascular Drug Reviews 2007 Spring;25(1):1-13

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C; Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA : the journal of the American Medical Association 2007 Mar 28;297(12):1319-31

Read the Layperson version here.

Cancer Treatment Today » New Drugs

Nexavar in non-small cell lung cancer – pro

SAMSA – A New Drug for Low Sodium – pro