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Closing in on the 'Big C'

Author: Barbara Boughton

The battle against the disease that John Wayne once called the “Big C” has been ongoing for more than 100 years, but clinicians now have more exact and powerful therapies than ever before to aim against the illness. In the past few years, we’ve seen several key advances, including shorter, more convenient, and more potent therapies for cancers such as those of the breast, prostate, and colon; new diagnostic tests that can predict patients’ response to cancer treatments such as chemotherapy; and new drugs that harness the immune system.

While new treatments provide patients with increased survival, they also carry other benefits that include faster recovery and, often, fewer side effects. Here we look at some of the major advances that are changing the cancer landscape and offering welcome hope.

A personalized approach

Our understanding of cancer has progressed to the point that we are on the cusp of being able to individualize therapy to each patient—and thus achieve the greatest benefit and the least risk—as clinicians are increasingly able to choose treatments based on the genomics, or “genetic fingerprint,” of each unique tumor. In fact, genomics—the study of tumors to understand which genes are important in the development of specific cancer types and their metastasis—is one of the most promising areas of cancer research today.

Advances in cancer genomics have led to the discovery of mutated genes in breast and colon cancers, for example, which has led to the creation of tests that can determine which treatments (such as chemotherapy) may be most effective for certain cancers. In addition, research in this area has led to targeted treatments such as Gleevec® (imatinib mesylate), for chronic myeloid leukemia, gastrointestinal stromal tumors, and other cancers, and Herceptin® (trastuzumab), for breast cancers containing a mutation that causes tumors to have too much of the protein HER2.

“Research into the genetics or genomics of cancer, especially in those complex diseases where there are no known effective therapies, is an area that’s revolutionary,” says Maurie Markman, MD, senior vice president for clinical affairs at Cancer Treatment Centers of America® (CTCA). “As well as being actively used and investigated at CTCA and other medical centers around the country, the science of cancer genomics will advance so much in the next few years that it will change how we think about and select therapies for patients. In my opinion, in two to five years we’ll be regularly obtaining genetic analyses of tumors and making treatment decisions based on those analyses.” New therapies developed through cancer genomics and individualized for patients’ unique needs will provide cancer patients with improved outcomes, longer survival, and decreased side effects. “This is absolutely the future of cancer treatment,” says Dr. Markman.

Novel treatments

New therapies—including immunotherapies and targeted treatments that attack and kill tumor cells with greater precision than ever before—are providing hope for patients facing difficult-totreat cancer.

Immunotherapy

Immunotherapy treatments for cancer have shown a great deal of promise in the past few years with the advent of two new drugs that have been approved by the US Food and Drug Administration (FDA): Provenge® (sipuleucel-T) for prostate cancer and Yervoy® (ipilimumab) for melanoma.

Provenge is used for men with prostate cancer that has spread beyond the prostate and is no longer responding to hormonal treatment but who still have minimal symptoms. Often described as a vaccine, Provenge uses the patient’s own immune system cells, which are activated to knock out other white cells in the body that normally dampen immune system response.

Yervoy, the first drug available to help late-stage melanoma patients extend their survival, is a monoclonal antibody—a type of manmade protein— that blocks an important switch on some immune cells. Cancers activate this switch to weaken the body’s immune response to tumors. In a pivotal clinical trial of 676 late-stage melanoma patients for whom all other treatments had failed, those taking Yervoy survived 10 months after treatment versus six months for those taking an experimental vaccine.1 The drug has also been tested in advanced melanoma in combination with DTICDome® (dacarbazine), a chemotherapy now used for metastatic melanoma, in previously untreated patients. A clinical trial of 502 patients with previously untreated metastatic melanoma showed that the combination of Yervoy with DTICDome compared with DTIC-Dome alone improved survival at one, two, and three years.2 Yervoy is not yet FDA approved for previously untreated metastatic melanoma patients, however.

“Although research on immunotherapy for cancer has been going on for more than a century, there’s a real enthusiasm for both Provenge and Yervoy because they’re some of the few successful and effective immunotherapies now on the market,” says David Berd, MD, national director for immunotherapy at CTCA. “Provenge gives us another option for some men with prostate cancer that has spread. In the case of Yervoy, it gives us an effective treatment, although not a cure, for advanced melanoma patients for the first time,” he adds.

Preventing and treating bone disease

There are also new and effective treatments that slow the thinning and the weakening of bone (osteoporosis) and can help prevent fractures, which can result from the spread of cancer or from cancer treatments. Bone fractures, which are of high concern in cancer treatment, can occur in the spine as well as in joints, resulting in pain and immobility.

“Not only do bone abnormalities cause pain, but when a bone fractures, a patient may lose the ability to walk or use an arm for a long period of time. That has a real impact on a patient’s quality of life,” Dr. Markman says. Because it takes a long time for a fracture to heal, patients may be immobile and confined to bed, putting them at risk for major complications such as blood clots, he adds.

The good news is that osteoporosis can now be successfully treated with a number of therapies, including a new drug that has proven very effective in preventing skeletal fractures. For bone disease, clinicians may use drugs called bisphosphonates, which slow the rate of bone thinning, reduce new bone damage, and promote bone healing, according to the American Society of Clinical Oncology (ASCO). Selective estrogen receptor modulators like Evista® (raloxifene) also strengthen bone. The new targeted agent Xgeva® (denosumab) was also FDA approved in November 2010 to help prevent skeletal fractures in patients whose cancer has spread to and damaged bone. Xgeva is a monoclonal antibody that targets RANKL, a protein in the body that is involved in cancer-related bone destruction.

Intraoperative radiation therapy

One of the most recent advances in the treatment of breast cancer is the use of single-dose intraoperative radiation therapy (IORT) as an alternative to traditional radiation after surgery. IORT does not take as long as traditional radiotherapy, recovery is faster, and it’s more cost-effective, Dr. Markman notes.

When IORT is used to treat breast cancer, radiation is aimed at the tumor bed—the area around the tumor that has just been removed—while normal tissue is shielded from the intensity of the radiation dose. This strategy, Dr. Markman says, enables clinicians to apply high doses of radiation in a short period of time without harming normal tissue. By contrast, conventional radiation must be performed over a longer period of time because the radiation dose must be lower to leave normal tissue unscathed, so effective treatment takes longer.

Proton therapy

Another exciting treatment advance that the oncology community is watching closely is proton therapy—a type of radiation that uses positively charged particles rather than X-rays. Protons, which are positively charged particles that are part of an atom, can destroy cancer cells at high energy, according to ASCO.

Proton therapy is delivered through a machine called a cyclotron, which speeds up the protons and deposits them around the tumor. Although traditional radiation can damage normal tissue around the tumor, protons’ energy is more likely to target the tumor site, resulting in lower radiation doses to surrounding normal tissues, according to ASCO. The radiation dose in proton therapy can be as much as 60 percent lower than in X-ray therapy for the same cancer, with similar effectiveness and less risk of side effects such as skin reactions and fatigue. Proton therapy is currently being used for treatment of cancers such as those of the prostate, breast, and lung and in retinoblastoma, a cancer of the eye that affects children.

“One of the biggest advantages of protons is that we can guide them to the area we want to treat without causing as much damage to normal tissue as traditional radiation, so patients suffer fewer side effects,” says William Hartsell, MD, medical director of the for-profit Central Du- Page Hospital (CDH) Proton Center, a ProCure Center in Warrenville, Illinois. He notes, however, that proton therapy is useful only for those cancers that have not spread beyond the primary organ or lymph nodes.

The CDH Proton Center has been open for only nine months, but clinicians there have treated nearly 200 patients, including those with brain tumors and prostate cancer. “Proton therapy is especially good for tumors in children because the therapy is so much safer and affects less normal tissue,” Dr. Hartsell says. One downside to proton therapy, however, is that it’s not accessible for many patients. Right now only a handful of medical centers offer proton therapy because it requires a cyclotron, a machine that costs tens of millions of dollars, as well as stable buildings with thick concrete foundations to provide stability for the cyclotron, Dr. Hartsell says.

Dr. Markman says that CTCA is considering offering proton therapy to its patients, as it would enable more-focused radiation at lower doses with fewer side effects. “It’s much more expensive and more complicated than traditional radiation, but the idea behind it is that you get the same effects with less radiation. So there’s potential for equal efficacy as compared with traditional radiation— with less toxicity.”

Making strides to improve quality of life

As our understanding of cancer has advanced, researchers have also been able to illuminate the true benefits—in terms of improved survival and better quality of life—of differing invasive procedures such as surgeries. New research in breast cancer, for instance, suggests that some women with early-stage breast cancer don’t need surgical removal of many lymph nodes (vessels near the breast containing fluid that provides breast tissue with fullness and moisture).

Because lymph nodes are near the breast, cancer in the breast can easily spread there. Cancer that has spread to the lymph nodes also tends to be more aggressive. So, in the past, any sign of cancer meant that a woman would undergo surgery to remove many lymph nodes. But the removal of a large number of lymph nodes often leaves women with a condition called lymphedema, which results from the buildup of lymph fluid in the arm and results in pain and swelling.

Now, however, an important clinical trial has revealed that surgical removal of many lymph nodes in women with earlystage breast cancer who have just a small amount of cancer in the sentinel lymph node or nodes (the nodes nearest the tumor) does not extend survival.3 Removal of just the sentinel lymph nodes means that a woman is less likely to experience lymphedema.

Progress continues

The advances outlined here offer a glimpse of the valuable progress that has been made—and which continues—in cancer research and treatment. Advances such as genomic analysis of tumors, new therapies that treat bone disease during cancer, and IORT for breast cancer are important leaps forward in the battle against cancer, as are strides made in improving quality of life—all of which should offer us hope as we look ahead.

References

  1. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine. 2010;363(8):711-23.
  2. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. New England Journal of Medicine. 2011;364(26):2517-26.
  3. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs. no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. Journal of the American Medical Association. 2011;305(6):569-75.
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