The American School of Oncology™ is pleased to announce the newest clinical information tool designed for physicians and nurses to support the treatment and management of your patients with renal cell cancer (RCC). The Renal Cell Cancer Resource Center^SM is a toll-free “call center” for community oncologists and nurses. Through this unique resource, physicians and nurses can easily access RCC experts to discuss the diagnosis, treatment, and management issues related to RCC. The most current information about administration and potential toxicities of treatments will be readily available.

To access the Renal Cell Cancer Resource Center, simply call our toll-free number (1-866-370-2722) and leave a brief message with your contact information. Nationally recognized physician experts are available to reply to your inquiry within 24-48 hours and are prepared to discuss your simplest and most complex issues. If you prefer to make initial contact via internet, access the Renal Cell Cancer Resource Center website at www.info4rcc.com to leave your contact information.

Advances and Challenges in Targeted Therapies: The last meeting of this series is scheduled for November 4 in St. Louis. This series of meetings will provide updates related to the use of targeted agents in the treatment of the leukemias and a variety of solid tumors. See www.nmcr.com for more information and to register online.

FDA Actions:

On October 17, 2006 the FDA approved sanofi-aventis’ docetaxel (Taxotere®) for use in combination with cisplatin and fluorouracil prior to radiation therapy for the induction treatment of patients with inoperable, locally advanced squamous cell carcinoma of the head and neck (SCCHN). The approval was based on data from the EORTC 24971/TAX 323 phase III trial involving 358 patients which demonstrated that patients receiving docetaxel fluorouracil plus cisplatin and fluorouracil (TPF), as compared to those treated with the standard regimen of cisplatin and fluorouracil (PF), experienced a significantly longer median progression-free survival (PFS) of 11.4 months vs. 8.3 mo. (p=0.0077, HR 0.71). Median overall survival was also significantly longer in the TPF arm (18.6 mo.) than in the PF arm (14.2 mo.) with a HR of 0.71 and a 29% risk reduction of death (p=0.0055).

On October 11, 2006 the FDA granted approval for a labeling extension for Genentech’s bevacizumab (Avastin®), administered in combination with carboplatin and paclitaxel, for the initial systemic treatment of patients with unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC. This recommendation is based on the demonstration of a statistically significant improvement in OS (primary endpoint) in patients receiving bevacizumab with carboplatin and paclitaxel (median 12.3 mo) compared to those receiving the chemotherapy alone (10.3 mo; HR 0.80, p=0.013) in a trial (E4599) of 878 patients. Although a consistent effect was observed across most subgroups, evidence of a survival benefit was not observed in women (HR 0.99).

On October 6, 2006 the FDA granted approval to Merck’s vorinostat (Zolinza™), a histone deacetylase inhibitor administered orally, for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or recurrent disease during or following two systemic therapies (one of which must have contained bexarotene). The approval was based on results from two studies involving a total of 107 patients with refractory CTCL that demonstrated an overall objective response rate of 30%, an estimated median response duration of 168 days, and a median time to tumor progression of 202 days.

On September 29, 2006 the FDA approved two additional uses for Genentech’s rituximab (Rituxan®) for the treatment of patients with low-grade or follicular, CD20-positive, B-cell NHL. One new indication for rituximab is for the first-line treatment of previously untreated patients with follicular NHL in combination with CVP chemotherapy. The second new indication is for the treatment of low-grade NHL in patients with stable disease or who achieve a partial or complete response following first-line treatment with CVP chemotherapy.

On September 27, 2006 the FDA granted accelerated approval to Novartis Pharmaceuticals’ imatinib (Gleevec®) as a single agent for the treatment of pediatric patients with newly diagnosed Ph+ CML. Approval is based upon the induction of both hematologic and cytogenetic responses. Complete hematologic response was observed in 78% and complete cytogenetic response rate was 65%, comparable to the results observed in adult CML patients.

The FDA last month granted approval to Amgen Inc.’s panitumumab (Vectibix™), an anti-EGFR monoclonal antibody, for the treatment of patients with EGFR-expressing metastatic colorectal cancer with disease progression on or following fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy regimens. The approval is based on the results of a trial involving 463 patients randomized to either best supportive care (BSC) alone or BSC plus panitumumab (P). The mean PFS was 96 days for patients receiving P plus BSC compared to 60 days for those on BSC only. No difference in OS between the two study arms was seen.

GlaxoSmithKline has announced the submission of a new drug application (NDA) to the FDA for approval to market lapatinib ditosylate (Tykerb®), in combination with capecitabine (Xeloda®), for the treatment of patients with advanced or metastatic HER2-positive breast cancer who have received prior therapy including trastuzumab. Lapatinib has been granted fast-track status by the FDA in this patient population. A phase III randomized trial of 324 women with advanced or MBC with documented HER2 overexpression demonstrated that the combination of lapatinib and capecitabine nearly doubled the median TTP (36.7 weeks) vs. capecitabine alone (19.1 weeks).

Wyeth Pharmaceuticals has initiated its global filing strategy for temsirolimus (Torisel™) with the simultaneous submissions of a NDA to the FDA and a marketing authorization application to the European Medicines Agency (EMEA). The company is seeking an indication for the treatment of patients with advanced renal cell carcinoma (RCC) for the drug that specifically inhibits the mTOR kinase that regulates cell proliferation, cell growth, and cell survival in cancer. The applications contain interim data from a phase III trial of 626 patients with previously untreated RCC. The primary endpoint was OS. Results demonstrated that treatment with temsirolimus increased the median OS time by 3.6 months, or 49%, compared with treatment with interferon-alpha.

MGI Pharma has received an approvable letter from the FDA for Saforis (glutamine) Powder in UpTec for Oral Suspension, an investigational therapy for the treatment and prevention of oral mucositis related to mucotoxic cancer therapy. The FDA has requested an additional phase III trial to evaluate the efficacy of Saforis in the proposed indication. A NDA, submitted in June and accepted for priority review, was based on phase III trial results of 326 patients with breast cancer who received anthracycline-based chemotherapy. The primary endpoint of the trial, defined as a reduction in the incidence and severity of oral mucositis, was met. Saforis, an oral formulation of glutamine delivered by MGI’s proprietary UpTec system, is designed to deliver high concentrations of glutamine into the damaged oral mucosa in order to promote healing and prevent damage to the oral mucosa.