Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Indications -- Cancer -- Ignore unavailable to you. Want to Upgrade?

To: Biomaven who wrote (59)	5/16/2001 1:07:18 PM
From: keokalani'nui	Respond to of 1840

Have noticed from time to time the experiments with hyperthermia and electric stimulation of tumors. Thought this was interesting and, if it is successful, is just perfect for JNJ to exploit. Hyperthermia (HT) + Doxil Significantly Enhances Drug Delivery and Efficacy in Metastatic Breast Cancer of the Chest Wall (CW): a Phase I/II Study. John W. Park, Paul Stauffer, Chris Diederich, Gail Colbern, Alison Lozner, Dmitri Kirpotin, Hope Rugo, Nancy Valente, Patricia Sneed, UCSF, San Francisco, CA; ALZA Corp, San Francisco, CA. Sterically stabilized liposomal doxorubicin (Doxil) preferentially accumulates in tumor tissue due to enhanced vascular permeability and retention within tumors. We previously showed in preclinical studies that HT can further facilitate Doxil accumulation in tumors by 3-fold, with consequently improved antitumor efficacy. Based on these results, we initiated the first ever Phase I/II study of HT + Doxil in patients with metastatic breast cancer of the CW. 23 patients have been enrolled, all of whom had failed prior therapies including radiation (21) and chemotherapy (22; mean number of regimens for CW metastases = 2.7). Patients received HT via 16-element planar array microwave or ultrasound applicators. Minimum, T90, and mean temperatures reached median values of 41.4, 42.2, and 42.7 °C, respectively. 1 h post-HT, patients received Doxil at 45 mg/m2 i.v., with HT/Doxil repeated every 28 days for 4-6 cycles. HT/Doxil was well-tolerated, with toxicities fully consistent with expected effects of either HT or Doxil alone. Grade 2 toxicities included PPE (3), mucositis (1), neutropenia (2), and thermal burn (2); 1 patient had Grade 3 congestive heart failure. To date, 20 patients are evaluable for response. In heated tumors, there was 1 CR (also a pathologic CR) and 11 PR (60%). In 17 patients with additional CW tumors outside the HT region, there were 6 PR (35%) due to Doxil alone. In 5 patients with evaluable distant metastases, there were no responses (0%). In the 17 patients with both heated and non-heated tumors, response in heated tumor vs.non-heated tumor was superior in 8 (47%), equivalent in 8 (47%), and inferior in 1 (6%); hence, HT was associated with improved efficacy (p=0.04, bidirectional sign test). FNA biopsies of heated CW tumor vs. non-heated CW tumor vs. normal tissue were assayed for doxorubicin uptake by scanning confocal microscopy. Drug uptake was increased in tumor vs. normal tissue, and further increased with HT. We conclude that sequential HT + Doxil significantly increases drug delivery and antitumor efficacy in patients with metastatic and refractory breast cancer of the CW.