Breast Cancer

Taxanes are the most active drugs in the treatment of metastatic breast and ovarian cancer. Weekly therapy with paclitaxel produces notable activity, with remarkably low toxicity.

This phase I study was undertaken to define the maximum tolerated dose, the dose-limiting toxicity, and the recommended dose of UFT plus leucovorin and vinorelbine in combination treatment of patients with metastatic breast cancer previously treated with one chemotherapy regimen. The pharmacokinetics of UFT and vinorelbine were also evaluated.

This article describes the design and early results of an open-label, nonrandomized phase I/II trial of oral UFT plus leucovorin therapy in combination with bolus injections of epirubicin and cyclophosphamide in patients with advanced or metastatic breast cancer. This study was designed as a cohort dose-escalation study with the principal aims being to determine dose-limiting toxicity, overall toxicity, maximum tolerated dose, tumor response, and time to disease progression.

CANTON, Ohio-Neoadjuvant breast cancer therapy research has revealed that “epirubicin has good activity in the neoadjuvant setting and was associated with prolonged survival in four studies, although this remains to be confirmed,” Terry Mamounas, MD, stated. Dr. Mamounas, Medical Director at Aultman Memorial Hospital in Canton, Ohio, spoke at the clinical investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology.

NEW YORK-“The number one question that I used to get as a clinician taking care of people with breast cancer and people worried about breast cancer was about hormone replacement therapy. Now, by far, the number one question is about soybeans,” said Larry Norton, MD, chief of Breast Medicine and head of the Division of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center.

MUNICH, Germany-‘‘Epirubicin-containing regimens significantly prolong relapse-free and overall survival rates compared with standard regimens” for treating breast cancer, Michael Untch, MD, reported at a clinical investigators’ workshop. ‘‘The dose-response relationship for epirubicin,” he continued, “translated into significant improvements in outcome, and dose-intensification of epirubicin and paclitaxel was well tolerated.”

ROCHESTER, Minnesota-Researchers have begun to suspect that estrogen might be important not only for its receptor-mediated effects but also because it may exert genotoxic effects, reported James N. Ingle, MD. “There is evidence that estrogen genotoxicity may play a role in breast cancer development. That is, in the course of metabolism of estrogen, semi-quinones and quinones are formed, which can result in depurinating DNA adducts,” Dr. Ingle stated.

WASHINGTON-Stanford University researchers have developed a device for gene comparison that could lead to a more exact way to categorize cancer tumors and assess the survival chances of patients. In initial experiments with breast cancer patients, they detected specific gene combinations in tumors and found that certain combinations indicated either a good or bad prognosis.

PISA, Italy-‘‘Anthracycline/taxane combinations given upfront should be the new standard of care for metastatic breast cancer,” Pierfranco Conte, MD, said at a clinical investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology. Dr. Conte is chief of the Division of Medical Oncology at St. Chiara Hospital in Pisa, Italy.

TORONTO-Epirubicin (Ellence) and doxorubicin (Adriamycin) in combination regimens for adjuvant treatment of breast cancer will be compared in a major randomized controlled trial sponsored by the National Cancer Institute of Canada (NCIC), according to Maureen Trudeau, MD, head of systemic therapy at Sunnybrook Regional Cancer Centre in Toronto, Ontario. Dr. Trudeau described the reasoning behind and the design of NCIC CTG-MA.21 at a clinical investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology.

NEW ORLEANS-Premenopausal women with breast cancer who receive goserelin (Zoladex) have an increased event-free survival over 5 years, regardless of whether they also receive tamoxifen (Nolvadex) or have had prior chemotherapy. This key finding from 5-year follow-up of the Zoladex in Premenopausal Patients (ZIPP) trial was presented at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO).

Initial data from a phase II study of exemestane (Aromasin) as first-line treatment of advanced breast cancer in postmenopausal women suggest that the new agent may extend the time that patients remain free of tumor growth compared to tamoxifen (Nolvadex).

ATLANTA-In a retrospective review of more than 12,000 screening mammograms, computer technology found 52% of missed cancers, Kunio Doi, PhD, reported at the Era of Hope meeting, featuring research sponsored by the US Department of Defense Breast Cancer Research Program.

PISA, ITALY-Gemcitabine, epirubicin, and paclitaxel (GET) is a highly active regimen in previously treated metastatic breast cancer, Pierfranco Conte, MD, reported at a clinical investigators’ workshop sponsored by the University of Texas M. D. Anderson Cancer Center and Pharmacia Oncology. Dr. Conte is Chief of the Division of Medical Oncology at St. Chiara Hospital in Pisa, Italy.

AstraZeneca announced recently that the US Food and Drug Administration (FDA) has approved use of its breast cancer drug tamoxifen (Nolvadex) to reduce the risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) following breast surgery and radiation.

CANTON,Ohio-Occult micrometastases may still be present after the standard 5 years of tamoxifen adjuvant hormonal treatment for patients with stage I or II breast cancer and receptor-positive tumors. Some of those micrometastases may be estrogen- or tamoxifen-sensitive, stated Terry Mamounas, MD, adding that this is a major reason the National Surgical Adjuvant Breast and Bowel Project (NSABP) has undertaken clinical trial NSABP B-33. The trial will compare 2 years of exemestane (Aromasin) to 2 years of placebo in postmenopausal, estrogen receptor-positive stage I-II breast cancer patients who are disease free after being on tamoxifen (Nolvadex) for 5 years.

Adjuvant chemotherapy represents a significant advance in the management of early-stage breast cancer and, as such, has saved many lives. Worldwide, adjuvant chemotherapy has benefitted all groups tested, including

Adjuvant chemotherapy represents a significant advance in the management of early-stage breast cancer and, as such, has saved many lives. Worldwide, adjuvant chemotherapy has benefitted all groups tested, including

Adjuvant chemotherapy represents a significant advance in the management of early-stage breast cancer and, as such, has saved many lives. Worldwide, adjuvant chemotherapy has benefitted all groups tested, including

Adjuvant chemotherapy represents a significant advance in the management of early-stage breast cancer and, as such, has saved many lives. Worldwide, adjuvant chemotherapy has benefitted all groups tested, including

Capecitabine (Xeloda) is a new, orally administered, enzyme-activated fluoropyrimidine carbamate designed to generate high levels of fluorouracil (5-FU) in tumor cells. Selective tumor activation of 5´-deoxy-5-fluorouridine,

Capecitabine (Xeloda) is a new, orally administered, enzyme-activated fluoropyrimidine carbamate designed to generate high levels of fluorouracil (5-FU) in tumor cells. Selective tumor activation of 5´-deoxy-5-fluorouridine,

HER2 is a member of the type I tyrosine kinase growth factor receptor family and participates in normal growth control mechanisms. It is overexpressed or amplified in 20% to 30% of breast cancers, as well as other carcinomas. HER2 overexpression is associated with adverse prognostic indicators in primary breast cancer, and a number of reports have shown that HER2-overexpressing breast cancer is linked to an increased rate of recurrence/metastases, and therefore, decreased disease-free and overall survival rates.

Abstracts #317 and #322 attest to the high degree of antitumor activity of docetaxel (Taxotere) in the management of locally advanced breast cancer. In abstract #317 the authors tested two hypotheses: first, that the administration of a non–cross-resistant cytotoxic regimen after induction or neoadjuvant chemotherapy improved the outcome of combined-modality treatment for both responders and nonresponders to neoadjuvant chemotherapy; and second, that the addition of docetaxel to a standard, anthracycline-containing regimen improved both clinical and pathologic response rates in locally advanced breast cancer.

Gemcitabine (Gemzar) has emerged from its initial clinical evaluation in patients with metastatic breast cancer as an effective antitumor agent. Its usual schedule of administration is weekly, and it is a very well-tolerated regimen. In combination with anthracyclines, the activity matches that of other commonly used multidrug regimens, including CMF (cyclophosphamide [Cytoxan, Neosar]/methotrexate/fluorouracil) or FAC (fluorouracil/doxorubicin [Adriamycin]/cyclophosphamide). When the taxanes became the most effective agents against breast cancer, two-drug and three-drug combinations with gemcitabine were initiated. This development was stimulated by the need to discover effective, non–cross-resistant regimens for patients previously exposed to anthracyclines and classical alkylating agents.

In abstract #403 the combination of docetaxel (Taxotere) and doxorubicin was tested in a prospective, multicenter, phase II trial, by one of the foremost breast cancer research cooperative groups-the National Surgical Adjuvant Breast and Bowel

Doxorubicin and docetaxel (Taxotere) are two of the most effective drugs in metastatic breast cancer when used in monotherapy. The objective of this study was to investigate the toxicity and efficacy of the use of both drugs in full doses and sequentially in patients with metastatic breast cancer with no previous chemotherapy.

A phase I trial demonstrated that monthly docetaxel (Taxotere) and weekly gemcitabine (Gemzar) had both acceptable toxicity and encouraging antineoplastic activity in patients with previously treated advanced breast cancer. This phase II trial will determine the efficacy and toxicity of this regimen in advanced breast cancer patients who have measurable disease refractory to, or relapsed after, first-line or adjuvant chemotherapy.

Epirubicin (Ellence) is currently being studied in combination with the taxanes, such as docetaxel (Taxotere), in patients with advanced breast cancer. As a single agent, docetaxel has proven to be a very active drug in breast cancer, so the results of these combination trials are awaited with interest. Our experience has shown epirubicin/docetaxel to be a feasible and active combination in breast cancer.

The most efficacious primary chemotherapy regimens used to treat breast cancer contain anthracyclines. Unfortunately, a significant proportion of breast cancers fail to respond to such therapy. Therefore the aims of this study were (1) to determine the efficacy of primary docetaxel (Taxotere) in patients that initially fail to respond to anthracycline-based primary chemotherapy, and (2) to compare the efficacy of docetaxel with anthracycline-based primary chemotherapy in patients that are initially responsive to such therapy.