ONCOLOGY Vol 16 No 5

A new study conducted by researchers at the Mayo Clinic shows that samarium-153 lexidronam (Quadramet), approved by the US Food and Drug Administration (FDA) in 1997 for the treatment of pain in patients with metastatic bone lesions, can be used at higher doses to treat osteosarcoma. The results of the study were published recently in the Journal of Clinical Oncology (20:189-196, 2002).

The 4th Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops has been to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan (CPT-11, Camptosar).

The US Food and Drug Administration (FDA) has granted a 6-month priority review status to the supplemental new drug application filed by the AstraZeneca corporation for the use of anastrozole (Arimidex) in the adjuvant treatment of early breast cancer in postmenopausal women.

The limited effectiveness of currently available chemotherapy in the treatment of advanced esophageal cancer, and the poor survival achieved in locally advanced disease with combined chemoradiotherapy with or without surgery, have prompted the evaluation of new agents. Irinotecan (CPT-11, Camptosar) has promising single-agent activity in gastrointestinal cancers.

Topoisomerase inhibitors have been widely studied for the treatment of refractory or recurrent cervical cancer. Various schedules have been used, with response rates ranging from 13% to 20%. The combination of cisplatin and irinotecan (CPT-11, Camptosar) is being studied in cervical cancer.

Ovarian cancer, the second most common gynecologic malignancy, accounts for approximately 14,000 deaths annually in the United States. Disease relapse after primary treatment, which consists mainly of surgery followed by platinum-based therapy, occurs in more than 60% of ovarian cancer patients overall, and in more than 80% of those diagnosed initially with advanced-stage disease.

We conducted a phase II study to assess the response rate and toxicity profile of the irinotecan (CPT-11, Camptosar) plus cisplatin combination administered weekly to patients with at least one previous chemotherapy for advanced adenocarcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach or gastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 50 mg/m² of irinotecan plus 30 mg/m² of cisplatin, both administered intravenously 1 day a week for 4 consecutive weeks, followed by a 2-week recovery period.

Early clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect.

Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease.

The US National Cancer Institute Gastrointestinal Intergroup has contributed to the development of chemotherapy and radiation regimens for the treatment of stage II and III rectal cancer. The first Intergroup trial demonstrated improvement in relapse-free and overall survival for patients who received protracted venous infusion fluorouracil (5-FU) with radiation compared to those treated with bolus 5-FU.

Using a day 1 and 8, every-3-week schedule, our purpose was to determine the maximum tolerated dose of irinotecan (CPT-11, Camptosar) that can be administered immediately after gemcitabine (Gemzar) at a dose of 1,000 mg/m² IV. In this phase I trial, the maximum tolerated dose was defined as the dose level immediately below the level in which two of the first three patients in any cohort, or at least two of six patients in any expanded cohort, experienced dose-limiting toxicity. Dose-limiting toxicity pertained only to toxicity during the first cycle of treatment. Escalation of irinotecan was planned in groups of three patients, with three additional patients added at the first indication of dose-limiting toxicity. A total of 19 patients have been enrolled.

Over the past decade, patients with locally advanced rectal cancer at The University of Texas M. D. Anderson Cancer Center have been managed with preoperative chemoradiation. Patients achieving a complete clinical response to preoperative chemoradiation have had better pelvic tumor control, sphincter preservation, and overall survival than those with gross residual disease. Some patients achieving a complete clinical response have even had rectal-preserving surgery (full-thickness local excision).

Investigators from Memphis found that cancer patients who experience breakthrough pain require additional medical services that result in higher medical costs than those incurred by cancer patients without breakthrough pain. The study, published in the February 2002 issue of the Journal of Pain, reported that patients with breakthrough pain (perhaps two-thirds of this population) require more frequent hospitalizations and doctor visits than cancer patients without breakthrough pain. Patients who suffered from breakthrough pain incurred costs of approximately $12,000 a year for medical services specific to their pain (hospitalizations, emergency room, and physician visits), whereas patients who did not have breakthrough pain (but still experienced pain) incurred costs of approximately $2,400 a year.

Investigators recently reported the results of a study suggesting the benefits of identifying subgroups of breast cancer patients at high risk for hospitalization due to febrile neutropenia. Once identified, granulocyte colony-stimulating factor (G-CSF, Neupogen) might be administered prophylactically to these patients to help decrease the incidence of the side effect. The data were presented at the 24th annual San Antonio Breast Cancer Symposium.

The journal Lancet recently published an important analysis from six physicians at Weill Cornell Medical College (359:404-406, 2002), rebutting an article published in an earlier issue of Lancet (358:1340-1342, 2001) that cast doubt on the value of mammography in preventing death from breast cancer.

President Bush announced changes in the medical records privacy rule proposed by President Bill Clinton before he left office. Physicians do not have to comply with these rules until 2003.

The National Marrow Donor Program (NMDP) has published the 2001-2002 Transplant Center Access Directory-a free resource for all patients who are undergoing a blood stem cell transplant and do not have a matching donor in their family.

Elias Zerhouni, MD, nominated by President Bush to the position of director of the National Institutes of Health, is a leading researcher in cardiovascular imaging.

A fundamental assumption of lung cancer screening is that small tumors are less likely to have metastasized than large tumors. However, in a new study conducted at Duke Comprehensive Cancer Center, researchers showed that size does not necessarily indicate the severity of the cancer.

Abbott Laboratories recently announced the launch of AxSYM Plus, an enhanced version of its AxSYM automated immunoassay instrument system.

The combination of irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) produced a 1-year survival rate of 27%, which is greater than that reported for gemcitabine alone in previous studies in patients with advanced pancreatic cancer (15% and 18% 1-year survival rates, respectively). These study results were published in a recent issue of the Journal of Clinical Oncology (20:1182-1191, 2002).

Studies of a new treatment strategy for colorectal cancer using a therapeutic cancer vaccine technology have begun enrolling patients at several trial sites around the United States and Canada.

New research presented at the 93rd annual meeting of the American Association for Cancer Research (AACR) suggests that monitoring with the serum HER2/neu oncoprotein test may help oncologists assess the effect of trastuzumab (Herceptin)-based therapy in patients with metastatic breast cancer.

In their review of the history of the management of stage I/II Hodgkin’s disease, Drs. Ng and Mauch describe the results of various treatment protocols and outline the questions posed by ongoing European, Canadian, and American trials. In a broad sense, the questions posed by these trials will help clinicians understand the benefits and complications of these treatments. However, as clinically oriented as they are, the current studies have yet to answer some common problems faced by private practitioners-the clinicians who, in North America, manage most patients with Hodgkin’s disease.

The authors are to be complimented on a thoughtful and complete review of the application of the sentinel node paradigm to colorectal cancer. This paradigm is inherently quite different for colorectal cancer because, except for the occasional demonstration of variant anatomy, the technique will not alter the extent of surgery as it has done in melanoma and breast cancer.

The 5-year survival of patients with locally advanced squamous cell cancers of the head and neck is still less than 30%. Treatment of these cancers involves significant functional impairment, diminished quality of life, and considerable time and expense. Local recurrence and distant metastases are still fairly common, and the development of second primary cancers has a significant impact on survival in patients with initial early-stage disease. Despite the success of combination chemoradiation in locally advanced head and neck cancers, these facts stress the need for improved treatment of this disease.

The article by Drs. Gates and Kaplan provides an excellent review of malignancies associated with human immunodeficiency virus (HIV)-1 disease and chronicles the epidemiologic changes seen during the past 5 years. The literature review is very thorough and well balanced.

I read with interest the article by Hanks and colleagues-and the reviews that followed-on the evidence for cure in prostate cancer.

A dramatic spike in the incidence of Kaposi’s sarcoma (KS) in never-married men in New York and California in 1981 was one of the first indications of a new disease now known as acquired immunodeficiency syndrome (AIDS). We now appreciate a number of mechanisms by which human immunodeficiency virus (HIV) infection contributes to the pathogenesis of these tumors. The article by Drs. Gates and Kaplan provides an excellent review of changes in the epidemiology, presentation, and treatment of these tumors since the development of potent combination anti-HIV therapy.

Identification of targets in tumor cells vs normal cells (or at least a differential in their expression) is certainly a promising method for approaching the treatment and, indeed, the prevention of cancer. Presently, targeting of patient tumor cells has taken on even greater importance and interest with the discovery of the new agent imatinib mesylate (STI571, Gleevec), which is targeted to a kinase present in chronic myeloid leukemia (CML) cells (p210 BCR-ABL abnormal cells), which is required for CML cells to survive, but is not present in normal leucocytes.[1] The results with this agent targeted to the p210 BCR-ABL tyrosine kinase are indeed spectacular. The agent is of even greater interest in that it also works against some gastrointestinal stromal sarcomas with gain of function mutations in c-kit (CD117).[2] This activity of a targeted agent against a solid tumor increases the interest in targeted therapy to an even greater degree.