ONCOLOGY Vol 13 No 11

A three-day interdisciplinary cancer conference will be held March 2 through 4, 2000, at the Best Western Gateway Grand in Gainesville, Florida. The seminar will emphasize the latest advances in radiation therapy techniques and results. It will include refresher courses by senior faculty, panel discussions, and new departmental research results. Visiting Professor will be Professeur Jean-Pierre Gerard, Service de Radiotherapie-Oncologie, Hôpitaux de Lyon, France. Other presentations will be made by clinicians from the University of Florida Department of Radiation Oncology.

The findings of two clinical studies of C225, a monoclonal antibody (epidermal growth factor receptor inhibitor) being developed by ImClone Systems (New York City), were presented at the 1999 annual meeting of the American Society of Clinical Oncology (ASCO). The studies demonstrated the effectiveness of C225 in eliciting a clinical response in patients with advanced head and neck cancer when used in combination with standard radiotherapy and chemotherapeutic agents.

The National Cancer Institute (NCI) is about to embark on a series of “quality care” initiatives designed to identify the best medical care approaches for various cancers. The NCI strategy was laid out to the Senate Cancer Coalition by Robert Hiatt, MD, PhD, on September 16. Hiatt, who is the deputy director of the Division of Cancer Control and Population Studies at the NCI, disclosed that the NCI will be issuing a request for applications (RFA) for consortiums of investigators, presumably composed of oncologists, cancer centers, university medical centers, state cancer registries, and medical associations. Each team will be provided with core support to carry out innovative, in-depth analyses consistent with a series of recommendations made in the past year by both the National Cancer Policy Board and the President’s Cancer Panel. These recommendations include: developing a cancer data system that provides quality benchmarks for use by systems of providers; supporting national studies of newly diagnosed cancer patients, which yield data that relate care to outcomes; and trying to find out why some population segments are not receiving quality cancer care.

I enjoyed the review of malignant mesothelioma by Drs. Sean Grondin and David J. Sugarbaker that appeared in the July 1999 issue of oncology. On page 920, the authors mention that mesothelioma will recur locally at sites of pleuroscopy or thoracoscopy. From a radiation therapy standpoint, it is worth bringing to the readers’ attention that a small, prospective trial published by Boutin et al in Chest (108[3]:754-758, 1995) showed that radiotherapy to these sites prevents entry tract metastases. A radiation dose of 21 Gy in three fractions given 10 to 15 days after thoracoscopy decreased the incidence of entry tract metastases from 40% to 0%. This regimen should be considered for patients who will not receive a more definitive surgical procedure and adjuvant radiotherapy.

The American Society of Clinical Oncology (ASCO) applauded patient protection legislation passed recently in the US House of Representatives that would provide much-needed improvements in cancer patients’ access to high-quality care and treatment, including therapies offered in clinical trials. The Bipartisan Consensus Managed Care Improvement Act (HR 2723), introduced by Representatives Charlie Norwood (R-GA) and John Dingell (D- MI), passed by a vote of 275 to 151.

For many women under 40 years of age with breast cancer, surgery to remove the cancerous lump and accompanying radiation therapy seem to be the best option for eradicating the disease and preserving the natural breast. However, for women who carry a damaged version of the BRCA1 or BRCA2 gene, thus predisposing them to breast cancer, such treatment may be insufficient. Researchers at Jefferson Medical College have found that these women are at greater risk years later of either relapsing or developing new tumors than are similarly treated women who do not carry one of these genes.

This article by Yao, Shimada, and Ajani accurately describes the current state of the art of adjuvant therapy for gastric cancer. The authors’ primary conclusion and current recommendations are as follows:

The article by Olson and Pienta is a thorough review of the important issues facing men with metastatic prostate cancer and their caregivers. Many recent reports have documented physicians’ lack of awareness about cancer pain, which underscores the significance of proper evaluation and management. As the authors note, any evaluation of current and future therapies must focus not only on the efficacy of pain control but also on how a particular treatment affects a patient’s overall quality of life.

Yao and colleagues present a concise, yet complete review and analysis of adjuvant therapeutic approaches for gastric adenocarcinoma. They confirm a fact known to all clinical oncologists who manage patients with resected gastric cancer: No adequate data support the value of postoperative (adjuvant) or preoperative (neoadjuvant) therapy in managing patients with locally advanced adenocarcinoma of the stomach.

This two-part article by Krieg and Hoffman, published last month and concluded in this issue, explores the current management of penile cancer (part 1) and urethral cancer in both men and women (part 2). My remarks will focus on female and male urethral cancer.

In a recent poll of the American people, cancer was cited as the disease that most Americans (53%) feared would end their lives. Even though heart disease is 50% more likely than cancer to cause an American to die, it is the concern of only 37% of Americans. Among the African-American community, 78% believe that cancer is a major problem, and 17% believe it is a minor problem. Of American women, 40% are very worried that they may develop breast cancer.

In this two-part article, Krieg and Hoffman review the management of patients with cancer of the penis and those with cancer of the urethra, respectively. Both of these cancers are uncommon, and, when they present as small, early, circumscribed lesions, both can be cured (with organ preservation) by radiation therapy. Also following organ preservation by radiation therapy, these patients must continue to be followed closely because 25% to 35% will develop a local recurrence and can be cured by prompt salvage surgery.

Gastric carcinoma is a discouraging disease. Although we can clearly identify patient- and tumor-related variables that predict outcome, the only reproducible treatment- related variable associated with an improvement in survival is a complete (R0) resection.[1]

Haigh et al provide thoughtful, detailed summary of 3 decades of intensive work aimed at developing active, specific immuno-therapies (vaccines) for patients with melanoma. However, as the 20th century draws to a close, the key question is: Can any vaccine be considered an effective therapy for patients with melanoma? To rephrase the question: What constitutes proof of efficacy for a melanoma vaccine, and have any vaccines met those criteria? In a word, the answer to the first question is “no.” The answer to the second question, however, requires more elaboration.

Cancer treatments often cause sexual dysfunctions that remain severe long after therapy is over. Nevertheless, sexual counseling is not routinely provided in most oncology treatment settings. Most patients and their partners can benefit from brief counseling that includes education on the impact of cancer treatment on sexual functioning; suggestions on resuming sex comfortably and improving sexual communication; advice on how to mitigate the effects of physical handicaps, such as having an ostomy, on sexuality; and self-help strategies to overcome specific sexual problems, such as pain with intercourse or loss of sexual desire. Brief counseling can be provided by one of the allied health professionals on the oncology treatment team. A minority of patients will need specialized, intensive medical or psychological treatment for a sexual dysfunction. In a large cancer center, such treatment could be provided as part of a reproductive health clinic serving the special needs of cancer patients. In smaller settings, the oncologist should build a referral network of specialists. Not all managed care organizations reimburse for these services, however. [ONCCOLOGY 13(11):1585-1591, 1999]

In organizing this brief, but informative review of human melanoma vaccines, Haigh et al have provided an important service to the readers of oncology and are to be commended for their efforts. Their descriptions of the variety of vaccine technologies currently under development and their assessment of the strengths and weakness of each are, for the most part, fair and conservative.

Often overshadowed by more common genitourinary cancers, such as prostate, testicular, and kidney cancers, penile and urethral cancers nonetheless represent difficult treatment challenges for the clinician. The management of these cancers is slowly evolving. In the past, surgery, often extensive, was the treatment of choice. Recently, however, radiation and chemotherapy have begun to play larger roles as initial therapies, with surgery being reserved for salvage. With these modalities in their treatment armamentarium, oncologists may now be able to spare patients some of the physical and psychological sequelae that often follow surgical intervention without compromising local control and survival. Part 1 of this two-part article, published in last month’s issue, dealt with cancer of the penis. This second part focuses on cancer of the urethra in both females and males. [ONCOLOGY 13(11):1511-1520, 1999]

Cancer treatments often cause sexual dysfunctions that remain severe long after therapy is over. Nevertheless, sexual counseling is not routinely provided in most oncology treatment settings. Most patients and their partners can benefit from brief counseling that includes education on the impact of cancer treatment on sexual functioning; suggestions on resuming sex comfortably and improving sexual communication; advice on how to mitigate the effects of physical handicaps, such as having an ostomy, on sexuality; and self-help strategies to overcome specific sexual problems, such as pain with intercourse or loss of sexual desire. Brief counseling can be provided by one of the allied health professionals on the oncology treatment team. A minority of patients will need specialized, intensive medical or psychological treatment for a sexual dysfunction. In a large cancer center, such treatment could be provided as part of a reproductive health clinic serving the special needs of cancer patients. In smaller settings, the oncologist should build a referral network of specialists. Not all managed care organizations reimburse for these services, however. [ONCCOLOGY 13(11):1585-1591, 1999]

Gastric cancer is often advanced and unresectable at diagnosis. Even when a curative resection is possible, the 5-year survival rate for patients with T2 or higher tumors is less than 50%. Survival rates are even lower if lymph node metastases are present at surgery. Many phase III trials of adjuvant therapy have been conducted around the world during the past 4 decades, but their interpretation varies in the East and West. In the West, postoperative treatment modalities have not proven to be superior to postsurgical observation alone. Thus, at present, the routine use of postoperative therapy should be discouraged. In the Orient, however, routine use of postoperative chemotherapy and/or immunotherapy is common after a surgical procedure. Further investigations that correlate treatment response with molecular markers are needed. Improved clinical trial designs, including better preoperative staging, standardized surgical techniques, inclusion of adequate numbers of patients, and the continued use of a surgery-alone control group, are essential. In addition, the incorporation of newer active agents, radiotherapy, and new strategies, such as preoperative therapy and selection of patients based on tumor biology, would result in much-needed advances. Less toxic approaches with novel mechanisms of action, such as antiangiogenesis therapy, tumor vaccines, monoclonal antibodies, and matrix metalloproteinase inhibitors, also hold promise. [ONCOLOGY 13(11):1485-1494, 1999]

Investigation into the therapeutic use of vaccines in patients with metastatic melanoma is critically important because of the lack of effective conventional modalities. The most extensively studied melanoma vaccines in clinical trials are whole-cell preparations or cell lysates that contain multiple antigens capable of stimulating an immune response. Unfortunately, in the majority of studies, immune responses to these vaccines have not translated into a survival advantage. Advances in tumor cell immunology have led to the identification of candidate tumor cell antigens that can stimulate an immune response; this, in turn, has allowed for refinements in vaccine design. However, the exact tumor antigens that should be targeted with a specific vaccine are unknown. The univalent antigen vaccines, which have greater purity, ease of manufacturing, and reproducibility compared with polyvalent vaccines, may suffer from poorer efficacy due to immunoselection and appearance of antigen-negative clones within the tumor. Novel approaches to vaccine design using gene transfection with cytokines and dendritic cells are all promising. However, the induction of immune responses does not necessarily confer a therapeutic benefit. Therefore, these elegant newer strategies need to be studied in carefully designed clinical trials so that outcomes can be compared objectively with standard therapy. If survival is improved with these vaccine approaches, their ease of administration and lack of toxicity will firmly entrench active specific vaccine immunotherapy as a standard modality in the treatment of the melanoma patient.[ONCOLOGY 13(11):1561-1574, 1999].

The editor of Breast Cancer is Daniel F. Roses, MD, a professor of surgery at New York University and director of the Comprehensive Breast Cancer Center at that institution. Its contributors include Pat Borgen, MD, from Memorial Sloan-Kettering, Armando Giuliano, MD, from the University of California, Alison Estabrook, MD, from St. Luke’s Roosevelt Hospital, Frea Schnabel, MD, from Columbia-Presbyterian, David Page, MD, from Vanderbilt University, Larry Norton, MD, from Memorial Sloan-Kettering, and John Neiderhuber, MD, from the University of Wisconsin Medical Center. All of these notable individuals have made significant contributions to the management of patients with breast cancer.

Prostate cancer is the most commonly diagnosed cancer among American men. The majority of patients with advanced disease have metastatic bone lesions, which are frequently very painful. These lesions tend to respond well to treatment with both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, although careful dose titration and individualized treatment plans may be needed to achieve maximal analgesia. Opioid side effects are often transient or well controlled with additional medication. Patients with intolerable side effects may experience fewer adverse reactions with a different opioid. Palliative radiation provides pain relief in up to 80% of prostate cancer patients with single or at most a few sites of localized bone pain. Bisphosphonates, powerful inhibitors of osteoclast-mediated bone resorption, are promising new agents for the treatment of painful bone lesions in prostate cancer patients. Radioisotopes, which deliver high-dose radiation to bone lesions without significantly affecting normal bone, are highly effective in providing some degree of pain relief in up to 80% of patients with diffuse, painful bone metastases. Also, chemotherapy shows promise in alleviating pain and possibly extending survival in patients with advanced prostate cancer.[ONCOLOGY 13(11):1537-1549, 1999]

Dr. Schover’s review of counseling strategies for cancer patients regarding changing sexual function reflects her many years as a clinical therapist and researcher in this area. Her article describes the common failure of clinicians to address the sexual health concerns of cancer patients, and provides a comprehensive approach to this problem for use in the oncology clinical setting.