Solid advances against cancer hailed at ASCO

Since cancer is the No. 1 area for drug research, it's no coincidence that more than 400 targeted compounds are in development and scores were touted at the recent annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta. Below is a sampling of promising new or improved cancer fighters:

In announcing interim data from a pivotal phase III study of its dual tyrosine kinase inhibitor Tykerb (lapatinib) in advanced breast cancer, GlaxoSmithKline (GSK) showed that the oral agent plus capecitabine (Xeloda, Roche) nearly doubled time to progression compared with capecitabine alone.

Out of a total 392 patients in the study, 321 had refractory advanced or metastatic HER2-positive breast cancer, and neither standard chemotherapy nor Herceptin (trastuzumab, Genentech) worked any longer.

Lapatinib was studied separately as possibly warding off brain metastases-a complication in fully one-third of metastatic breast cancer patients. The preliminary results were hopeful but not definitive, and more studies are ongoing.

GSK plans to apply this year for approval of lapatinib. Currently, the firm offers a program for needy women to receive the drug free.

A new vaccine against cervical cancer not only prevents two other types of gynecologic cancers but may play a role in certain head and neck tumors, a report from the ASCO meeting revealed. Investigators showed that Gardasil (quadrivalent human papillomavirus [HPV] vaccine, Merck) was 100% effective in heading off vaginal and vulval cancers associated with HPV. The vaccine already has been hailed for preventing cervical cancer, which kills about 250,000 women a year worldwide.

Starting four years ago, researchers randomly assigned 18,000 females age 15 to 26 to receive either three doses of Gardasil or a placebo over a six-month period. During the next two years, 24 women on placebo developed vaginal or vulval precancers compared with none who were vaccinated.

"In human disease, there has never been a vaccine this effective," said lead investigator Jorma Paavonen, M.D., professor and chief in the department of obstetrics and gynecology, University of Helsinki in Finland, who presented the study. Gardasil prevents infection with two strains of HPV that cause cancer and two others that cause anal and genital warts, he explained.

The virus has also been found in cancers of the tongue, tonsils, and pharynx, according to a new study from the University of Wisconsin. This suggests that head-and-neck cancer may be connected with the two deadly HPV strains.

In June the Food & Drug Administration approved Gardasil to prevent cervical cancer. (For more on Gardasil, see page 13.)

Researchers at ASCO reported that an experimental agent able to induce apoptosis, or programmed cell death, may one day help treat a broad range of solid tumors and hematologic malignancies. The novel agent, called Apo2L/TRAIL, is being codeveloped by Amgen and Genentech as a potential cancer therapeutic in non-small cell lung cancer; melanoma; sarcoma; and cancers of the colon, prostate, and breast; as well as leukemia and lymphoma.

"Although our phase I data are early, we may have here a whole new class of targeted agents," said oncologist Roy Herbst, M.D., Ph.D., professor, University of Texas M.D. Anderson Cancer Center, Houston. "Apo2L/TRAIL is designed to activate pathways inside tumor cells that lead to cell self-destruction." Ordinarily, he explained, when normal cells are damaged or unneeded, apoptosis eliminates them. "But apoptosis is missing in cancer cells, which allows them to thrive."

Although this was a safety study, the test drug halted tumor growth in more than half the 58 patients with a variety of advanced cancers. They received up to eight cycles of intravenous (IV) Apo2L/TRAIL at dose levels ranging to 15 mg/kg.

Also found: Among 37 patients whose cancers could be assessed, 22 (60%) had stable disease after four cycles, while four (10%) had at least stable disease after eight cycles. Most patients reported drug-related fatigue and diarrhea, none dose-limiting, said Herbst.