Cancer Medications : Sterile Talc Powder, Sutent

by National Cancer Institute

(Page 14 of 18)

Sterile Talc Powder

On December 15, 2003, the FDA approved Sterile Talc Powder™ (a trademark of Bryan Corporation), administered intrapleurally (within the pleural cavity) via chest tube, as a sclerosing agent to decrease the recurrence of malignant pleural effusions in symptomatic patients.

Malignant pleural effusion results from an accumulation of fluid in the pleural space, the area between the layer lining the chest cavity (parietal pleura) and the membrane covering the lungs (visceral pleura). It is a common complication of malignant disease, particularly in patients with advanced cancer.

The data demonstrating safety and efficacy are from the published medical literature. There were five randomized studies that were designed to evaluate the risk of recurrence of malignant pleural effusions in patients with a variety of solid tumors. For each study, talc slurry was compared with a concurrent control, using a prospectively defined objective measure of "success." For the 89 evaluable patients studied in the five randomized controlled trials, there was an 89 percent success rate (range 79-100 percent). Thirteen additional single-arm trials and retrospective series from the literature are also supportive of efficacy with variously defined "success" rates ranging from 75-100 percent.

Adverse events (AEs) most frequently reported in the literature in association with intrapleurally administered talc slurry are fever and pain. Acute pneumonitis and Acute Respiratory Distress Syndrome (ARDS) have been reported in association with intrapleural talc administration.

Sterile Talc Powder should be administered after adequate drainage of the effusion. The success of pleurodesis appears to be related to the completeness of drainage of the pleural fluid, as well as the full re-expansion of the lung. The recommended dose is 5 grams, dissolved in 50-100 milliliters of sodium chloride solution. Although the optimal dose for effective pleurodesis is unknown, 5 grams was the dose most frequently reported in the published literature.

The only other licensed formulation of talc (Sclerosol Intrapleural Aerosol™, also made by Bryan Corporation) is packaged with a chlorofluorocarbon (CFC) propellant for direct insufflation into the open pleural surface intraoperatively or during thoracoscopy.

Sutent

On January 26, 2006, the FDA granted approval for sunitinib malate (Sutent® capsules, made by Pfizer, Inc.), for the treatment of gastrointestinal stromal tumor (GIST) after disease progression on, or intolerance to, imatinib mesylate (Gleevec®).

Approval was also granted for the treatment of advanced (metastatic) renal cell carcinoma (kidney cancer) based on partial response rates and response duration under accelerated approval regulations. Postapproval trials in renal cell carcinoma are required to demonstrate clinical benefit such as increased survival or improvement in disease-related symptoms.

Like imatinib, sunitinib is a molecularly targeted therapy that binds to and inhibits tyrosine kinase proteins involved in a tumor's growth and blood supply. However, sunitinib binds to different as well as more kinase proteins than does imatinib.

Efficacy and safety in GIST patients were evaluated in a randomized, double-blind placebo-controlled trial in patients who had disease progression during prior imatinib treatment or who were imatinib-intolerant. The primary endpoint was time-to-progression (TTP).

Randomization into the treatment arms was 2:1; 207 patients were randomized to sunitinib and 105 to placebo. Baseline age, gender, race and performance status were comparable between the two treatment arms. Most patients enrolled (96 percent in both arms) had progressed on or within six months of completing prior imatinib therapy. Approximately 30 percent of patients were > 65 years of age and more than 98 percent had an Eastern Cooperative Oncology Group (ECOG) performance score of 0/1.

A planned interim efficacy and safety analysis was performed after 149 TTP events had occurred. A significant advantage for sunitinib in TTP (median 27 versus six weeks with p<0.0001; hazard ratio = 0.33) and an advantage in progression-free survival (median 24 versus six weeks with p<0.0001; hazard ratio = 0.33) were observed. Survival data are not mature.

A single-arm study conducted in GIST patients following progression on or intolerance to imatinib enrolled 55 patients following identification of the recommended phase II regimen. Five partial responses were observed (response rate 9.1 percent, 95 percent C.I. 3.0, 20.0).

Efficacy and safety in kidney cancer were evaluated in two single-arm, multicenter trials (Study 1 and 2) enrolling 169 patients with metastatic disease. All patients had either progressive disease or intolerance to interleukin-2 and/or interferon-alpha. The median age of patients enrolled on the two trials was 57 years (range 24-87); 65 percent were male.

All patients had an ECOG performance score of < 2 at screening. Ninety-five percent of the treated population had a component of clear cell histology and 97 percent had prior nephrectomy. Approximately half of the patients had three or more disease sites.

Overall response rate was the primary endpoint for both Study 1 and 2. No complete responses were observed. Study 1 had a 25.5 percent (95 percent CI 17.5, 34.9) partial response rate (core radiology laboratory assessment). Response duration is not mature. Study 2 had a 36.5 percent (95 percent CI 24.7, 49.6) partial response rate (investigator assessment). The median response duration was 54 weeks (95 percent CI 34.3, 70.1).

The most common treatment-emergent adverse events occurring more frequently in the sunitinib arm of the placebo-controlled GIST study included diarrhea, skin discoloration, mucositis/stomatitis, asthenia, and altered taste. Hypothyroidism was observed in 4 percent of patients receiving sunitinib; hypothyroidism was not observed on the placebo arm.

Grade 3/4 events that were more common with sunitinib included diarrhea, hypertension, and asthenia (weakness). Grade 3/4 treatment-emergent laboratory abnormalities occurring more commonly with sunitinib included neutropenia and thrombocytopenia. The safety profile in the kidney cancer single-arm trials was similar to that in the GIST randomized study.

Decreases in left ventricular ejection fraction have been noted with sunitinib. Dose reduction and/or addition of antihypertensive or diuretic medications may be required; spontaneous recovery has also been observed. Patients should be monitored for signs and symptoms of congestive heart failure and sunitinib should be discontinued if these are observed.

A small number of fatal and life-threatening tumor-related hemorrhages have been noted in patients receiving sunitinib. Elevations in amylase and lipase have been observed; pancreatitis has been observed rarely.

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