ONCOLOGY Vol 11 No 3

Researchers at Duke University Medical Center and the Durham V. A. Medical Center say the psychological impact of taking even a single puff of a cigarette on a preset "quit day" means a smoker will probably go back to smoking within 6 months.

In late January, the Agency for Health Care Policy and Research (AHCPR) released the first evidence report under its new evidence-based practice initiative. The report indicates that screening has been shown to be effective in detecting early-stage

Response to liarozole fumarate has been observed in patients with receptor-positive metastatic breast cancer, as well as those with receptor-unknown disease, confirming the biologic efficacy of this agent. The first clinical study of the role of liarozole in

A study of women with cervical intraepithelial neoplasia (CIN), a condition that often precedes invasive cervical cancer and is linked to infection with certain strains of human papillomavirus (HPV), found that those with the most extensive infections also

Public policy initiatives and increased physician awareness are needed to maintain a healthy balance between the promise of genetic engineering and the potential for genetic discrimination, a Stanford/Veterans Affairs (VA) physician maintains. His

Tumor growth is the result of two opposing processes--cell division and cell loss. As long as division outpaces loss, tumors will continue to grow. The form of "active" cell death called apoptosis is now known to be controlled by specific genes, and it is hoped that manipulating the expression of these genes could shift the balance in favor of cell loss.

In a lively session featured at the 32nd Annual Meeting of the American Society of Clinical Oncology (ASCO), Jerome P. Richie, MD, Brigham and Women's Hospital, Boston, and Steven H. Woolf, MD, MPH, Medical College of Virginia,

The incidence of ductal carcinoma in situ (DCIS) has increased dramatically since the advent of screening mammography in the 1980s. The age-adjusted DCIS incidence rates increased 17.5% annually from 1983 to 1992.[1] The percentage of patients with DCIS treated with mastectomy has decreased from 71% in 1983 to 44% in 1992. The percentage of patients with DCIS undergoing lumpectomy and radiation in 1992 was 23.3% and lumpectomy only was 30.2%.

In this article, Dr. Rich traces the evolution of chemoradiation in cancer of the rectum from its role as adjuvant therapy to its role in neoadjuvant therapy and its potential as definitive therapy. The efficacy of irradiation and fluorouracil (5-FU)-based

Dr. Rich presents a comprehensive overview of adjuvant therapy for advanced operable rectal cancer. He emphasizes the roles of infusional chemoradiation in both the adjuvant setting and as sole therapy. Unless otherwise specified, the following comments pertain to clinically resectable B2-C (T3, N0-N1) adenocarcinoma of the rectum.

In 1994, the results of a randomized intergroup trial coordinated by the North Central Cancer Treatment Group (NCCTG 86-47-51) indicated that protracted fluorouracil (5-FU) infusion during postoperative adjuvant radiation therapy results in

Quantitative radiation biology was revolutionized in 1956 when Puck and Marcus published the first cell survival curve, relating radiation dose to the fraction of cells surviving.[1] The term "survival" generated a great deal of discussion at that time and led to the definition of such terms as "reproductive death," "reproductive integrity," and "clonogenicity" (among others), all designed to explain that the end point of cell culture experiments is the loss of the cell's ability to divide indefinitely and produce a sizable visible clone.

In patients with an advanced disease or a terminal illness, it may become necessary to institute parenteral opioid therapy either on a temporary basis (for acute breakthrough pain) or permanently. Continuous intravenous or subcutaneous opioid infusions have been the mainstay of parenteral opioid therapy for oncologic pain. Patient-controlled analgesia (PCA) now offers an alternative modality, and Drs. Bruera and Ripamonti review the current status of this relatively new technique. Is there any evidence to suggest the superiority of one modality over the other for the treatment of oncologic pain?

The Van Nuys Prognostic Index (VNPI) is, in many ways, the best current approach for classifying patients with ductal carcinoma in situ (DCIS) according to their risk of local recurrence after breast-conserving therapy. However, this index has very important limitations.

Overexpression by the HER2 gene plays a significant role in breast cancer pathogenesis, and the phenomenon is commonly regarded as a predictor of a poor prognosis. HER2 overexpression has been linked to sensitivity and/or resistance to hormone therapy and chemotherapeutic regimens, including CMF (cyclophosphamide, methotrexate, and fluoro-uracil) and anthracyclines. Studies of patients with advanced disease demonstrate that, despite the association of HER2 overexpression with poor prognosis, the odds of HER2-positive patients responding clinically to taxanes were greater than three times those of HER2-negative patients. Further studies in preclinical models used combination therapy for breast cancer cells that overexpress HER2, and the use of agents that interfere with HER2 function plus paclitaxel (Taxol) resulted in significant antitumor effects. [ONCOLOGY 11(Suppl):43-48, 1997]

Clinical trials to develop paclitaxel (Taxol)-containing combinations started in 1992 with several approaches to combine doxorubicin and paclitaxel. Schedule-dependent toxicity limited doses in the initial trials, although antitumor activity was high. More recently, a well-tolerated, highly effective doxorubicin/paclitaxel regimen was developed with the use of bolus anthracycline administration and a 3-hour infusion of paclitaxel. Combinations of paclitaxel with cisplatin have provided mixed results. Paclitaxel combined with fluorouracil (5-FU) and folinic acid proved effective in patients with extensive prior chemotherapy; the addition of mitoxantrone (Novantrone) to this combination was feasible, well tolerated, and possibly enhanced the efficacy of paclitaxel and 5-FU. Combinations of paclitaxel with cyclophosphamide (Cytoxan, Neosar), vinorelbine (Navelbine), edatrexate, and radiation continue in clinical development. [ONCOLOGY 11(Suppl):29-37, 1997]

The use of adjuvant irradiation combined with systemic chemotherapy, or "chemoradiation," in the management of patients with operable rectal cancer has enabled more conservative surgery to be performed. Chemoradiation

Optimal dosing and scheduling are among the most important issues being addressed in clinical studies of the taxanes. The results to date indicate that there may not be a single administration schedule that produces optimal antitumor efficacy. Instead, the specific doses of the taxanes relative to each schedule and the overall aggressiveness of the dosing schedule should be considered. There appears to be a threshold taxane dose or concentration below which only negligible antitumor activity is observed, as well as a plateau dose or concentration above which no further antitumor activity occurs. The doses at which both threshold effects and plateauing of dose-response curves occur seem to be inversely proportional to the duration of the administration schedule. For paclitaxel (Taxol), it appears that comparable antitumor effects are achieved with both short (1- and 3-hour) and prolonged (24- and 96-hour) schedules as long as equitoxic dosing regimens are used. The majority of clinical studies with docetaxel have used a somewhat aggressive dosing schedule, 100 mg/m² over 1 hour, which marks the outer edge of the dosing envelope, but nonrandomized trial results suggest a dose-response relationship in the 60- to 100-mg/m² dosing range. [ONCOLOGY 11(Suppl):7-19, 1997]

The following position statement was made by the American Association for Cancer Research in response to the press release on mammography screening for women 40 to 49 years old issued by the National Institutes of Health

The proven safety profile and antitumor activity of paclitaxel (Taxol) in the treatment of metastatic breast cancer led investigators at Memorial Sloan-Kettering Cancer Center (MSKCC) to further examine the agent's potential in the treatment of advanced breast cancer. Efficacy and tolerability studies of paclitaxel as single-agent therapy were undertaken, along with parallel investigations of quality-of-life parameters. The studies examined the effects of 96-hour infusion schedules of paclitaxel and are currently assessing the feasibility of a weekly 1-hour infusion schedule. Researchers at MSKCC also compared the results of a variety of two- and three-drug paclitaxel-containing regimens to determine possible synergism and better define safety profiles. They examined the combination of paclitaxel and edatrexate, as well as a promising combination of paclitaxel and a monoclonal antibody directed at growth factor receptors. The latter ongoing trial will include both laboratory studies that examine possible cellular mechanisms for the combination's observed synergy and a clinical trial that combines paclitaxel with a monoclonal antibody directed against the epidermal growth factor. In conclusion, the investigators discuss the optimal integration of paclitaxel into doxorubicin/cyclophosphamide (Cytoxan, Neosar)-based adjuvant therapy for node-positive stage II-III resectable breast cancer. [ONCOLOGY 11(Suppl):20-28, 1997]

Apoptosis is a mode of cell death that is currently of intense research interest in developmental and cancer biology. For more than 40 years, radiobiologists have been aware of cells in irradiated specimens that display the

The extensively studied agent docetaxel (Taxotere) has shown marked clinical activity in the treatment of anthracycline-resistant breast cancer. Phase I trials indicate that toxicities, such as mucositis and neutropenia, limit the administration of docetaxel to shorter perfusion schedules. Pharmacokinetic studies have shown that docetaxel's clearance by hepatic metabolism is correlated with a marked increase in risk of toxicity in patients with impaired liver function. Nevertheless, studies of docetaxel as front-line therapy for breast cancer were initiated because of its good activity against tumors in early studies and its close relationship to paclitaxel (Taxol), an agent with proven efficacy. Phase II studies have demonstrated excellent activity for docetaxel as a single agent, with an overall response rate of 61% in trials of a 100-mg/m² dose. A phase III study is currently comparing docetaxel with paclitaxel as single-agent therapy. Docetaxel is expected to provide a better response rate but a higher incidence of neutropenia. The agent shows promise in adjuvant therapy, with very high response rates in anthracycline-resistant patients. Preliminary results of tests using docetaxel in combination with doxorubicin show high objective response rates but low complete response rates; early results suggest that this combination may have some advantages over paclitaxel/doxorubicin. [ONCOLOGY 11(Suppl):38-42, 1997]

Patient-controlled analgesia (PCA) is a relatively new technique in which patients are able to self-administer small doses of opioid analgesics when needed. Many different devices are available for opioid infusion, including

Despite the results of the National Surgical Adjuvant Breast and Bowel Project B-17, there continues to be debate regarding the most appropriate treatment for patients with ductal carcinoma in situ (DCIS) of the breast. Numerous clinical, pathologic, and laboratory factors can aid clinicians and patients wrestling with the difficult

By engineering proteins that coagulate the blood that feeds malignant tumors, scientists at UT Southwestern Center at Dallas have succeeded in destroying malignancies in mice. This therapy is expected to be effective against all major cancers, with

We read with interest the recent practice guidelines on prostate cancer published by the National Comprehensive Cancer Network (NCCN) in a supplement to the November 1996 issue of ONCOLOGY (pp 265-288). The establishment of such