Chemotherapy and Other Biologic Therapies
The Johns Hopkins Melanoma Program offers a broad range of expertise in novel approaches to the management of advanced melanoma as well as standard chemotherapy and other biologic therapies. Staff and faculty at Johns Hopkins have extensive experience in delivering complicated therapies such as high dose interferon and interleukin-2, and are designated regional centers treating larger volumes of patients with these therapies. In addition to well-established collaborations with national cooperative groups, Johns Hopkins faculty are building a translational research program to offer patients a wide variety of options that include studies of new therapies under development at Johns Hopkins. Our faculty also work closely with the National Cancer Institute, located 30 minutes from Baltimore, to offer pioneering clinical studies of emerging therapies that are not widely available to cooperative groups.
Expert multidisciplinary care is provided by Johns Hopkins faculty working together with colleagues in other specialty areas. Surgical oncologists at Johns Hopkins are integral team members available to discuss surgical options, even for the most advanced cancers (link to surgery). Interventional radiologists have broad experience in catheter placement and management, as well as radioablation techniques for certain metastatic lesions. Radiation oncology experts provide the latest techniques in irradiating lesions in most parts of the body, including difficult-to-treat tumors in the brain using non-invasive procedures with the Gamma Knife (link). Follow-up care for melanoma patients is carefully coordinated and includes a team of surgeons, medical oncologists and dermatologists.
For patients who have had surgery and have no evidence of residual melanoma, but are at significant risk for relapse, (generally include Stages II and III, options include careful observation, standard high-dose interferon and experimental therapies.
Johns Hopkins experts are established leaders in providing a complicated regimen of high-dose interferon, which is the only FDA-approved therapy for Stage IIb, IIc and III melanoma patients whose tumors have been surgically resected. Interferons are proteins that stop cell growth, blood vessel formation, and the protein-manufacturing process. They are classified into two types corresponding to the location of their genetic blueprints: Type I interferons have genes encoded on chromosome 9; and the genetic components of Type II interferons are found on chromosome 12. There are ongoing studies to determine the potential benefits of their properties. High-dose interferon adjuvant therapy for patients with melanoma was approved approximately ten years ago, but there remains debate among the medical community regarding the value of the therapy, especially since significant side effects can occur in many patients. Although it is and FDA-approved option, adjuvant interferon therapy is not generally accepted as standard-of-care. For some patients, benefits may include a delay of relapse by one year, but the effects on long-term survival are not defined at this time. Johns Hopkins experts offer high-dose interferon to appropriate Stage II and III patients whose disease has been surgically removed. The one-year therapy requires intensive dosage monitoring and adjusting, close observation of blood work, and attention to therapy-associated symptoms.
Treatments for Advanced Melanoma
Melanoma patients with Stage IV disease, which has spread to various parts of the body, or with unresectable Stage III (regional) disease have a variety of treatment options including FDA-approved chemotherapy drugs and biologic agents, as well as clinical trials to test emerging therapies. Dacarbazine (DTIC) is an intravenous chemotherapy drug typically offered to Stage IV patients which is administered every three weeks in an outpatient clinic or in the hospital. Temozolomide (Temadar) is an oral chemotherapy taken daily for six weeks. Temozolomide and DTIC are a class of compounds called DNA-alkylating agents, which work by adding an alkyl group to portions of DNA within cancer cells. These agents disrupt the ability of DNA to uncoil and separate, which, in turn, halts tumor cell division and growth. Both drugs can induce tumor regressions in 15-20% of patients with advanced melanoma, although many responses are only partial and not long-lasting.
Another standard treatment appraoch for advanced metastatic melanoma is high-dose interleukin-2. Interleukin (IL-2) is a hormone normally made by lymphocytes, which are blood cells that activates immune cells to fight cancer. IL-2 is a natural hormone found in the body, but a manufactured version has been developed for therapeutic use and is administered intravenously. Common side effects include: a temporary decrease in B-lymphocytes and platlets, nausea, vomiting, diarrhea, rash, liver and kidney complications and low blood pressure. All major organs of the body can be affected by IL-2 and the intensity of the side effects coincides with the dosage amount. It is offered to patients with advanced melanoma who are otherwise healthy. The high dose interleukin-2 regimen is a five-day inpatient treatment, which is repeated for several cycles depending on the tumor response. Results show that a 15-20% of patients respond to this treatment. A small number of patients undergoing this therapy achieve a complete remission, which can be long-lasting. Patients who have a complete response generally receive one additional course of IL-2 after their disease is gone. Those with stable disease do not have re-treatment beyond two courses of IL-2. Johns Hopkins is one of the few centers in the region equipped to give the therapy. Other institutions may need to administer the therapy in Intensive Care Units, but Johns Hopkins patients are able to undergo treatment in a private room in our well-equipped cancer center units, providing an improved environment. Johns Hopkins Kimmel Cancer Center nurses also receive special training to deliver this therapy.
Melanoma Program members also collaborate with other Johns Hopkins scientists, national cooperative groups and the National Ccancer Institute in developing and conducting studies of experimental therapies for patients who cannot receive or do not respond to high dose interleukin-2 or chemotherapy. Some studies involve experimental immunotherapy strategies that are being developed elsewhere or at Johns Hopkins. See more under Melanoma Research and Clinical Trials.