By Elizabeth Whittington

Revlimid Results Rewarding in Multiple Myeloma

A new derivative of Thalomid® (thalidomide) called Revlimid® (lenalidomide) has shown benefit to multiple myeloma patients whose myeloma progressed despite one prior therapy. The results of a phase III trial with Revlimid were so encouraging that the trial ended earlier than planned so researchers could offer Revlimid to all patients enrolled in the trial.

Patients with one prior therapy for recurrent or refractory multiple myeloma were either treated with Decadron® (dexamethasone), a steroid drug that has long been used for myeloma treatment, or Decadron plus Revlimid. Patients who received Revlimid with Decadron had their myeloma stay in remission nearly three times longer than patients treated with Decadron alone. After 15 months, 61 percent of patients taking Revlimid with Decadron had at least a 50 percent reduction in their myeloma as compared to only 15 percent of patients who got Decadron without Revlimid. Patients treated with Revlimid had their myeloma controlled for an average of 15 months compared to five months in patients on Decadron alone. A similar phase III trial with Revlimid in Europe also saw positive results in patients with myeloma.

Revlimid, an oral pill, belongs to the same class of drugs as thalidomide, but Revlimid produces fewer and less severe side effects than thalidomide. The main side effects of Revlimid are neutropenia, rash and fatigue.

Revlimid has also performed well in trials with myelodysplastic syndrome, a type of cancer that affects the bone marrow, and may be approved as soon as early 2006.

For more information, go to www.celgene.com.

New Approval for Velcade for Multiple Myeloma

The FDA has approved Velcade® (bortezomib) for multiple myeloma patients after only one failed chemotherapy regimen. The phase III trial that led to the approval showed greater benefit when patients were treated with Decadron plus Velcade compared with Decadron alone.

Velcade was previously approved for patients whose myeloma progressed after at least two prior regimens. First approved through the FDA’s accelerated process in 2003, this new approval allows patients to receive Velcade earlier in the course of their myeloma treatment.

Velcade works by inhibiting proteasomes, a complex of enzymes that help regulate cell growth by breaking down proteins in the cell (see Winter 2004). While normal cells recover quickly after Velcade blocks proteasome activity, the drug is lethal to myeloma cells and causes the cancer cells to die.

Patients whose disease progressed despite one or two prior therapies were given Velcade or Decadron, the standard treatment for multiple myeloma. Only 18 percent of patients on Decadron had a response compared with 38 percent of patients on Velcade. More impressive is that patients who received Velcade had a significantly longer survival time than with Decadron, confirming the ability of Velcade to make a significant impact in the outcome of patients with myeloma. Side effects of Velcade included neuropathy (nerve damage) and low platelet counts (thrombocytopenia).

For more information, visit www.velcade.com.

Sorafenib Deals Blow to Kidney Cancer

Positive results for sorafenib (BAY 43-9006) have led researchers to offer the drug to all patients enrolled in a phase III randomized trial for advanced kidney cancer, also called renal cell carcinoma. The trial was done to study whether sorafenib prolonged survival and delayed cancer growth in patients whose kidney cancer had progressed despite prior therapy.

Sorafenib is one in a class of new targeted agents for cancer that can be taken by mouth. It inhibits a number of targets inside the cancer cell, including the vascular endothelial growth factor (VEGF) receptor and a protein called Raf, which are both thought to be important for tumor growth.

Sorafenib was found to double the time kidney cancer remained under control, from 12 weeks for patients taking a placebo to 24 weeks for those taking sorafenib. There was some reduction in the size of the tumor with sorafenib in almost three quarters of patients, although less than 10 percent had their tumors shrink by 50 percent or more. The benefit of sorafenib was seen in both young and old patients as well as those whose cancer had spread to other organs. The trial is ongoing to determine overall survival benefit.

Sorafenib was well tolerated, and side effects included diarrhea, high blood pressure and rash. It was noted that there was not an increase in fatigue with sorafenib when compared with placebo.

The FDA granted fast-track status to sorafenib in March 2004, and the makers of the drug are currently preparing a new drug application for full approval of sorafenib in advanced kidney cancer. In the meantime, the drug is being made available through a treatment protocol for individuals with advanced kidney cancer who have not been previously treated with sorafenib. Interested patients should ask their physicians to call 866-639-2827 for more information.

For more about sorafenib, go to www.onyx-pharm.com.

Vaccine Could Wipe Out Cervical Cancer

Human papillomavirus (HPV) is a common sexually transmitted virus that is responsible for nearly all cases of cervical cancers (see CURE, Winter 2004). Although millions of women will contract HPV during their lifetime, few will actually develop cervical cancer. To protect the 10,000 women who develop cervical cancer each year in the United States, researchers developed an HPV vaccine called Gardasil™ that can reduce the risk of infection with certain strains of HPV, thus reducing the incidence of cervical cancer.

In a large phase III trial, women vaccinated with Gardasil had a reduction in the incidence of infection with HPV types 6, 11, 16 and 18. In addition, the development of abnormal cells in the cervix (cervical dysplasia) was reduced by up to 90 percent compared with women not receiving the vaccine. HPV 6 and 11 have been shown to cause abnormal Pap smears, which may necessitate additional medical tests. Women in the trial were vaccinated three times within a six-month period.

Merck, maker of the vaccine, hopes to get FDA approval for Gardasil in late 2005. Phase III data, which involve over 25,000 people worldwide, is expected at the end of the year and may help Gardasil’s case for approval. Although Merck has not developed a vaccination plan, the company proposes that it be administered at a young age before women become sexually active. GlaxoSmithKline and other pharmaceutical companies are developing similar HPV vaccines.

Panitumumab Delays Metastatic Colorectal Cancer Growth

A number of new targeted agents are offering hope to patients with advanced or metastatic colorectal cancer whose cancer has progressed despite standard chemotherapy. These include the monoclonal antibody Erbitux® (cetuximab), which was approved in March 2004 for patients whose cancer had progressed after standard chemotherapy. Panitumumab (ABX-EGF) is another monoclonal antibody that, like Erbitux, binds to the epidermal growth factor receptor (EGFR).

Panitumumab inhibits the EGFR, which regulates cell growth (see “Targeting Lung Cancer”). In a phase II trial, panitumumab caused at least 50 percent tumor shrinkage in about 9 percent of patients with advanced CRC. This activity is similar to Erbitux, but because panitumumab is a fully human antibody instead of part mouse, it causes less allergic reaction.

As with all other EGFR inhibitors, most patients in the trial developed a skin rash, but side effects of panitumumab were otherwise minimal. Panitumumab is being studied by itself as well as in combination with chemotherapy in patients with advanced colorectal cancer. The drug is also being studied in non—small-cell lung cancer and kidney cancer. To learn more about trials with panitumumab, go to www.clinicaltrials.gov.