By Amy D'Orazio, PhD and Kavita Maung, PhD

Lung Cancer

Double Trouble for Lung Cancer
For many years doctors have relied on the use of “doublets” to treat patients with lung cancer. These doublets, so called because they include two chemotherapy drugs, were based on the premise that if one chemotherapy drug was good, then two might be even better. Most of the doublets include Paraplatin® (carboplatin) or Platinol® (cisplatin) based on studies in the ‘80s that showed these agents could prolong survival for patients with advanced lung cancer.

Today, the most popular doublet used in the United States is the combination of Taxol® (paclitaxel) and Paraplatin. However, until recently studies had never conclusively shown that there was an advantage to using two drugs instead of only one. Addressing this issue was important because there was concern that using two drugs could lead to increased side effects as well.

To answer these questions the cancer research group Cancer and Leukemia Group B undertook a trial in patients with lung cancer to compare Taxol/Paraplatin therapy to therapy with Taxol alone. The results, presented at the 2002 ASCO meeting in May, showed that treatment with the doublet significantly improved survival over treatment with Taxol alone for these patients who had advanced disease. However, it was also seen that there was an increase in severe side effects as well, which could mean that some patients would not be able to tolerate doublet therapy.

Mesothelioma

A Roadblock to Tumor Growth
Malignant mesothelioma, closely associated with a history of exposure to asbestos, develops from the sac lining the chest (pleural cavity) or the abdomen (peritoneum). The incidence of malignant pleural mesothelioma in the Western world has increased and new chemotherapy agents are being tested since no standard therapy has emerged for the treatment of this disease.

Alimta™ (pemetrexed), which acts by inhibiting cellular proteins that stimulate cancerous cells to grow, is the first new agent for treatment of malignant mesothelioma to emerge in several decades. Early studies of Alimta alone or in combination with other standard chemotherapy agents such as Platinol® (cisplatin) or Paraplatin® (carboplatin) have been published and have shown that Alimta exhibits antitumor activity in patients with malignant mesothelioma.
The results of a large phase III trial in previously untreated patients with malignant pleural mesothelioma comparing cisplatin with or without Alimta were reported at the May 2002 American Society of Clinical Oncology (ASCO) meeting. Over 450 mesothelioma patients were enrolled in this study and were given treatment with either cisplatin alone or cisplatin and Alimta. Most patients received supplementation with folic acid and vitamin B12 to minimize side effects associated with Alimta. Patients treated with Alimta and cisplatin lived about 33% longer then the patients who received cisplatin alone. Alimta is not yet commercially available in the United States. More information about Alimta can be found at www.alimta.com.

Breast Cancer

Hormones, Pure and Simple for Treating Advanced Breast Cancer
On April 25, 2002 the FDA approved a new hormonal agent for the treatment of women with advanced-stage breast cancer that has become resistant to tamoxifen.

For many years the only anti-estrogen therapy available was Nolvadex® (tamoxifen). However, tamoxifen is not considered to be a “pure” anti-estrogen because it can have growth-stimulating effects on the endometrium, the lining of the uterus. Some patients develop resistance to the inhibitory effects of tamoxifen.

For many years, researchers looked for an alternative antiestrogen therapy, one that would be a “pure” anti-estrogen, lacking stimulatory properties. That search came to fruition with the FDA approval of Faslodex™ (fulvestrant), an agent that not only hinders the function of the hormone receptors on the breast cancer cells, but also causes these receptors to be destroyed. The approval of Faslodex was based on data which showed it was equivalent to another hormonal agent called Arimidex® (anastrozole). However, other data, recently released at the 2002 ASCO meeting, show that Faslodex may offer an additional advantage, the ability to prolong the time until the tumor progresses.
Faslodex is given by injection once per month and is expected to be widely available by the end of May 2002. Most of the side effects which are reported during treatment with Faslodex are mild and similar to those experienced during menopause, such as hot flashes. There is also a small risk of developing blood clots. Patients taking Faslodex, or any other hormonal agents should not smoke for this reason.

Additional studies are ongoing to determine if Faslodex is effective for women with advanced breast cancer who have not yet been treated with tamoxifen. To learn more about Faslodex, visit www.faslodex.com.

Colon Cancer

Triple Teaming Colon Cancer
Last year significant media attention was directed to a new combination of drugs that prolonged life for patients with colon cancer. Nicknamed “Triple Drug Therapy” this combination included Camptosar® (irinotecan), fluorouracil, and folinic acid (also known as leucovorin) and was one of the first regimens to demonstrate longer survival for patients with metastatic colorectal cancer.
Oxaliplatin is a newer agent currently being tested in colorectal cancer patients. It is administered as a short infusion every two or three weeks. At the 2002 ASCO meeting, Richard Goldberg, MD, from the North Central Cancer Treatment Group reported a trial which compared the Triple Drug Therapy regimen to a new regimen that included oxaliplatin with fluorouracil and folinic acid (known as Folfox). A preliminary analysis showed that Folfox could be a good option for advanced colorectal cancer, with good results seen in terms of producing tumor shrinkage, in prolonging the time until cancer progression, and in prolonging survival. Folfox was also associated with fewer side effects the Triple Drug Therapy, particularly severe diarrhea.

At this time the FDA recommends Triple Drug Therapy as its approved option for metastatic colorectal cancer patients. Oxaliplatin is approved for use only in Europe and Asia. However, trials in the United States that could lead to the approval of oxaliplatin are nearing completion and discussions are ongoing between the manufacturer and the FDA to make oxaliplatin available to more patients on a compassionate basis until the time where it is approved for widespread use.

For more information about the results of this clinical trial visit www.cancer.gov under “Colon and Rectal Cancer Updates” or see the ASCO website at www.asco.org.

Lymphoma

Custom-Made Therapy for Lymphoma
Anyone who has ever had anything custom-made knows that there is nothing that matches so well as something designed especially for you. But could the same be true of lymphoma therapy?

Lymphoma cells are special because they each carry a unique identifying protein, known as an idiotype, that is specific to the tumor cell, and specific to the person who has that cancer. Because of this, since the early ‘80s researchers have been able to make vaccines to stimulate the patient’s body to eradicate lymphoma. These vaccines are specific to one individual person’s tumor only, which causes that person’s immune system to attack and destroy lymphoma cells. However, the time and expense, as well as the difficulty in generating this therapy made it unattainable for many patients. Large scale clinical trials, which are required before the Food and Drug Administration could approve such an approach, were difficult to do.

However, a new technology, called Hi-GET™ could soon change all that. In the past vaccines required large biopsies from the patients from which they obtain live cells from which to create the vaccine. Hi-GET, a new way of developing patient-specific, anti-lymphoma vaccines, is efficient and makes generating lots of vaccines for many individual patients feasible because it requires a smaller biopsy sample from the patient and allows the researcher generating the vaccine to freeze the sample or manipulate it in whatever way necessary.
Lymphoma vaccines generated by Hi-GET were recently tested in a phase II trial and showed 67% of patients with low-grade lymphomas were able to develop specific anti-lymphoma immune responses. The vaccine prevented the patients’ disease from progressing for about 4.5 years, as compared to chemotherapy, which usually keeps disease under control between one to three years. Based on these results a phase III trial is ongoing that will study the efficacy of the lymphoma vaccine for patients with low-grade non-Hodgkin’s lymphoma.

For more information about this clinical trial e-mail ClinicalInfo@genitope.com or visit www.genitope.com.

Kidney Cancer

Cutting off the Food Supply to Kidney Cancer
Kidney cancer cells have a voracious appetite for nutrients and other factors in the blood, so maintaining a good blood supply is critical for the tumor to survive and grow.

Avastin™ (bevacizumab), a monoclonal antibody does just that by blocking the actions of VEGF, a substance that stimulates the growth of new blood vessels. By blocking VEGF, Avastin decreases the tumors blood supply, starving the tumor and potentially leading to decreased growth. Drugs like Avastin that block the growth of new blood vessels are known as angiogenesis inhibitors.
At the 2002 meeting of the American Society of Clinical Oncology, James Yang, MD, from the National Institutes of Health reported that Avastin, although it caused a reduction in tumor size in just 8% of the patients, was able to slow metastatic kidney cancer from progressing. The patients who received Avastin had their cancers under control for longer periods of time than the patients who took a placebo. The main side effects of Avastin are headache and increased blood pressure which is usually only seen at higher doses. At the doses used in this study, side effects were minimal.

In a second presentation at the 2002 American Society of Clinical Oncology meeting, Eric Rowinsky, MD reported that a second antibody therapy, called ABX-EGF was effective for patients with kidney cancer. ABX-EGF is a new antibody, which blocks cell growth through the EGF receptor, a protein expressed on kidney cancer cells which helps them grow uncontrollably. In this trial ABX-EGF was able to halt cancer growth or cause tumor shrinkage in half of the patients. The primary side effect was a mild skin rash. More data about this new antibody are expected in the early part of next year.

To learn more about Avastin in kidney and other tumor types, visit the Genentech website at www.gene.com. More information about ABX-EGF can be found at www.abgenix.com.