ONCOLOGY Vol 14 No 8 | Oncology

August 31, 2000

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.

August 31, 2000

Ever since the first phase II study of paclitaxel (Taxol) began, there has been ongoing controversy about the optimal dose and schedule of administration of this drug. The initial reports of marked antitumor activity against metastatic breast cancer were obtained using 250 mg/m² administered by 24-hour continuous IV infusion. This schedule was originally developed in an attempt to reduce the incidence and severity of anaphylactic reactions. Subsequent to the determination that this dose and schedule was effective and safe, there were multiple attempts to develop more convenient schedules, and dose/schedules associated with an improved side-effect profile.

August 31, 2000

Currently there are a number of available agents that are moderately active in non–small-cell lung cancer (NSCLC). These include cisplatin (Platinol), gemcitabine (Gemzar), vinorelbine (Navelbine), paclitaxel (Taxol), docetaxel (Taxotere), and irinotecan (Camptosar). How best to combine them, maximizing survival while minimizing toxicity, is the subject of intense investigation.

August 31, 2000

The Southwest Oncology Cooperative Group (SWOG) conducted a study in which single-agent docetaxel (Taxotere) was used as “consolidation” therapy following concurrent chemoradiotherapy (abstract #1916). A previous SWOG study (S90-19) (Proc Am Soc Clin Oncol 16: 446a [abstract 1600], 1997) established that chemotherapy with cisplatin (Platinol)/etoposide could be given concurrently with definitive thoracic irradiation both safely and effectively. In this earlier trial, following the completion of irradiation, two additional cycles of cisplatin/etoposide were given.

August 31, 2000

Gómez-Bernal et al (abstract #341) report the results of a docetaxel (Taxotere)/vinorelbine (Navelbine) combination as second-line therapy for metastatic breast cancer. Both agents were administered on the same day and repeated every 14 days. The 52% objective response rate is impressive, since vinorelbine alone would be expected to produce a 20%–30% response rate in this setting, with docetaxel projected to achieve a 40% complete and partial remission rate. Therefore, the results suggest an additive interaction between the two agents.

August 31, 2000

Over the past 5 years it has become evident that the administration of taxanes on a weekly schedule dramatically changes their toxicity profile, compared to the standard 3-weekly schedule. Weekly docetaxel (Taxotere) is markedly less

August 31, 2000

Evidence generated by controlled clinical trials over the past 4 decades indicated that combination chemotherapy produced superior results to single-agent cytotoxic therapy. Response rates and times to progression were superior with combination chemotherapy, and survival was also favorably altered by this approach. This paradigm has been recently challenged on the basis of the Norton-Simon hypothesis and by the development of more effective, new cytotoxic agents, specifically the taxanes.

August 31, 2000

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.

August 31, 2000

Before the introduction of the taxanes into the management of breast cancer, the anthracyclines (and doxorubicin and epirubicin [Ellence] in particular) were considered the most active agents against this malignancy. The marked activity of single-agent taxanes suggested that their antitumor efficacy might match and perhaps exceed that of the anthracyclines. Several prospective randomized trials have confirmed these initial impressions. At intermediate doses (60 mg/m²), the activity of doxorubicin and paclitaxel (Taxol) was similar; at higher doses (75 mg/m²), doxorubicin appeared more effective. Conversely, docetaxel (Taxotere) was reported to be more active than doxorubicin in one trial.

August 31, 2000

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.

August 31, 2000

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

August 31, 2000

In medically suitable patients with stage III (locally advanced) non–small-cell lung cancer, the use of cisplatin (Platinol)-based chemotherapy as induction therapy prior to definitive local therapy has been shown to improve survival (J Natl Cancer Inst 86:673-680, 1994; Ann Intern Med 125:723-729, 1996). This is true regardless of whether the local treatment modality used is surgery or thoracic irradiation. However, because cisplatin therapy is particularly toxic, there is interest in studying other agents in the induction setting. Given its activity in non–small-cell lung cancer, docetaxel (Taxotere) is one logical agent to investigate.

August 31, 2000

A meta-analysis of randomized controlled trials (Br Med J 311:899-909, 1995) has shown that the use of cisplatin (Platinol)-based combination chemotherapy in patients with good performance status leads to a modest improvement in median survival and an absolute increase in 1-year survival proportion of 10%. There are several different platinum-based regimens approved by the Food and Drug Administration for use in advanced non–small-cell lung cancer. Whether any one regimen is superior is unclear. A recent randomized controlled trial found no difference in median survival and quality of life between carboplatin (Paraplatin)/paclitaxel (Taxol)-the most commonly used regimen in the United States-and cisplatin/vinorelbine (Navelbine)-a regimen more popular in Europe and Canada (Proc Am Soc Clin Oncol 18: 461a [abstract 1777], 1999). The newer agents gemcitabine (Gemzar) and docetaxel (Taxotere) are among the most active single agents in non–small-cell lung cancer, and use of either in combination with cisplatin has shown promise.

August 31, 2000

These abstracts examine the use of single-agent docetaxel (Taxotere), an antimicrotubule agent and one of the most active drugs against NSCLC currently available, in the first- and second-line settings.

August 02, 2000

One hundred centers from Europe, the Middle East, Asia, and South America participated in a non–small-cell lung cancer (NSCLC) study with broad inclusion criteria (first and second line) to establish the toxicity and efficacy profile of docetaxel (Taxotere) at 100 mg/m² in worldwide clinical practice.

August 02, 2000

Docetaxel (Taxotere) is an active single agent in the treatment of non–small-cell lung cancer. Weekly administration of docetaxel minimizes myelosuppression and is generally well tolerated. To further evaluate the efficacy and toxicity of this novel schedule, we performed a phase II trial in patients with advanced non–small-cell lung cancer who were either elderly (age > 65 years) or poor candidates for combination chemotherapy due to coexistent illness or poor performance status.

August 02, 2000

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.

August 02, 2000

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.

August 02, 2000

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.

August 02, 2000

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.

August 02, 2000

This study was conducted to determine whether docetaxel (Taxotere) prior to definitive local treatment improves overall survival when compared to local treatment without prior chemotherapy in patients with radically treatable stage IIIA N2 (T0–3), T3 (N0-1) or IIIB non–small-cell lung cancer. Local treatment was defined at baseline.

August 02, 2000

The degree of pathologic response of tumor to primary chemotherapy is of considerable prognostic importance in patients with breast cancer. The addition of docetaxel (Taxotere) to an anthracycline-based primary chemotherapy regimen has been shown to result in significantly improved pathologic breast cancer response. The identification of predictors of treatment response will permit cytotoxic regimens to be tailored to individual patient requirements and permit pathologic response rates to be improved.

August 02, 2000

The aim of this study was to assess the efficacy and toxicity of the combination of docetaxel (Taxotere) and vinorelbine (Navelbine), every 15 days, in anthracycline-pretreated metastatic breast cancer patients.

August 02, 2000

Between June 1996 and March 1998, 429 first-line metastatic breast cancer patients were randomized to receive AT (doxorubicin [Adriamycin] 50 mg/m² and docetaxel [Taxotere] 75 mg/m²) or AC (doxorubicin 60 mg/m² and cyclophosphamide [Cytoxan, Neosar] 600 mg/m²), day 1 every 3 weeks for a maximum of eight cycles.

August 02, 2000

The combination of docetaxel (Taxotere) and doxorubicin is highly effective in breast cancer, but it presents relatively high hematologic toxicity. Recent data have suggested advantages for the weekly administration of docetaxel regarding the safety

August 02, 2000

The objective of this study was to assess the response rate and the toxicity of the combination docetaxel (Taxotere)/vinorelbine (Navelbine) in patients with advanced breast cancer.

August 02, 2000

The purpose of this study was to define the antitumor activity of the PGT (cisplatin [Platinol]/gemcitabine [Gemzar]/paclitaxel [Taxol]) combination in chemonaive non–small-cell lung cancer patients.

August 02, 2000

Docetaxel (Taxotere) and vinorelbine (Navelbine) are active agents in the treatment of metastatic breast cancer. Preclinical data suggest that there may be synergism between vinca alkaloids and taxane compounds. The current study evaluates the combination of docetaxel and vinorelbine with concurrent granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) in anthracycline-refractory breast cancer. The objectives of this study are to determine the response rate, time to progression, survival, and toxicities of this regimen.

August 02, 2000

The purpose of this trial was to evaluate the efficacy and safety of weekly gemcitabine (Gemzar) plus monthly docetaxel (Taxotere) (J Clin Oncol 16:3866-3873, 1998) as second-line treatment for non–small-cell lung cancer.

August 02, 2000

Weekly administration of taxanes as palliative treatment in metastatic breast cancer has been reported with significantly reduced hematologic toxicity and comparable efficacy to standard every-3-week protocols. This study update provides mature results with weekly docetaxel (Taxotere) in a larger patient population.

August 02, 2000

Increasing the dose density of active drugs by delivering maximum tolerated doses sequentially with minimal intervals between cycles could potentially increase response rate and benefit in metastatic breast cancer. We tested this hypothesis by assigning

August 02, 2000

Docetaxel (Taxotere)/cisplatin (Platinol) and docetaxel/gemcitabine (Gemzar) are active and well-tolerated chemotherapy regimens for the treatment of patients with advanced non–small-cell lung cancer (NSCLC). A phase II randomized trial was conducted in order to compare the efficacy and toxicity of these regimens.

August 02, 2000

Based on results from phase I studies, one of the recommended doses for doxorubicin/docetaxel (Taxotere) is doxorubicin 60 mg/m² plus docetaxel 60 mg/m² every 21 days. However, information on the efficacy and toxicity of this dose level in

August 02, 2000

Docetaxel (Taxotere) is a semisynthetic taxane that has efficacy in combination regimens with doxorubicin (Adriamycin) in the treatment of metastatic breast cancer. This study was instituted to assess the role of this combination in the neoadjuvant treatment of locally advanced breast cancer (LABC).

August 02, 2000

Designated E1594, this trial was designed to compare three platinum-based combination regimens containing third-generation drugs active against non–small-cell lung cancer to a reference regimen of cisplatin (Platinol) 75 mg/m² day 1 plus paclitaxel (Taxol) 175/mg/m²/24 h (arm A). The experimental regimens were as follows: gemcitabine (Gemzar) 1,000 mg/m² days 1, 8, 15 plus cisplatin 100 mg/m² day 1 (arm B); docetaxel (Taxotere) 75 mg/m² day 1 plus cisplatin 75 mg/m² day 1 (arm C); and paclitaxel 225 mg/m²/3 h day 1 plus carboplatin (Paraplatin) at an area under the concentration-time curve of 6 (AUC in mg/mL · min) day 1 (arm D). Arms A, C, and D were repeated every 21 days and arm B every 28 days.

August 02, 2000

From March 1996 to March 1998, 106 patients with untreated metastatic breast cancer (MBC) were treated with docetaxel (Taxotere) (100 mg/m²) and doxorubicin (75 mg/m²) on an alternating cycle-by-cycle (doxorubicin, docetaxel, doxorubicin, etc) or sequential (four cycles of docetaxel, then four cycles of doxorubicin) basis, every 3 weeks, for a maximum of eight cycles.

August 02, 2000

Results of the GEPARDO Trial: A Phase IIB Study Comparing the Combination of Dose-Intensified Doxorubicin and Docetaxel With or Without Tamoxifen in Patients With Operable Breast Cancer

August 02, 2000

We previously reported the efficacy of concurrent cisplatin (Platinol)/etoposide (PE) and radiotherapy in stage IIIB non–small-cell lung cancer in which biopsy confirmation of T4 (noneffusion) or N3 status was required (S9019). In view of the activity of docetaxel (Taxotere) as second-line therapy and potential molecular mechanisms of action favoring taxane sequencing, we designed the present study to maintain a core of concurrent PE/radiotherapy, but to substitute docetaxel consolidation for the two additional cycles of PE.

August 01, 2000

This book is the 17th volume in the Basic and Clinical Oncology series edited by Bruce D. Cheson, MD. Like other volumes in this series, Expert Consultations in Breast Cancer follows a unique format and seeks to integrate advances in the basic understanding of breast cancer with promising new therapies and changing health- care economics. The integration of these different perspectives provides both a conceptual and pragmatic framework for clinical decision-making.

August 01, 2000

A landmark research trial by the University of Wisconsin Comprehensive Cancer Center showed that chemotherapy offers survival benefits for advanced, non–small-cell lung cancer patients. The study, presented at the 36th annual meeting of the

August 01, 2000

The results of a multicenter, phase III metastatic breast cancer study indicates that, in women with previously untreated metastatic breast cancer, sequential chemotherapy induction using doxorubicin and docetaxel (Taxotere) is as effective and

August 01, 2000

The US Food and Drug Administration (FDA) has approved a novel, shorter administration regimen for Bristol-Myers Squibb’s paclitaxel (Taxol) injection for the treatment of advanced ovarian cancer. The FDA granted approval for this new

August 01, 2000

The initial reaction to President Clinton’s June directive on Medicare payment for patient care costs in clinical trials was extremely positive. Senators Jay Rockefeller (D-WV) and Connie Mack (R-FL), who have long and unsuccessfully pushed a

August 01, 2000

Data presented at the annual meeting of the American Society of Clinical Oncology further validated ChromaVision Medical Systems’ automated cellular imaging system (ACIS). The data from a collaborative study conducted by the United States National Institutes of Health, the Institute of Pathology in Basel, Switzerland, and two diagnostic companies, DAKO A/S and Vysis, Inc, documented that results of the ACIS HER2 immunohistochemical test correlate strongly with overall patient survival. Tests that provide information to help predict both the time and likelihood of survival are vital to clinicians in guiding critical treatment decisions.

August 01, 2000

Sen. Mack has been cochair of the Senate Cancer Coalition, so he was also quite happy that the Senate approved a National Institutes of Health budget for fiscal year 2001 (starting October 1) that would be a $2.7 billion increase over the

August 01, 2000

Chemotherapy is an integral part of treatment for patients with nasopharyngeal carcinoma. Chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease. In

August 01, 2000

Chemotherapy is an integral part of treatment for patients with nasopharyngeal carcinoma. Chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease. In

August 01, 2000

Chemotherapy is an integral part of treatment for patients with nasopharyngeal carcinoma. Chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease. In

August 01, 2000

Three-dimensional (3D) treatment planning refers to the use of software and hardware tools to design and implement more accurate and conformal radiation therapy. This is a major advance in oncology that should lead

August 01, 2000

This concise review by Drs. Wexner and Hwang examines the issues surrounding the use of laparoscopy in the management of gastrointestinal (GI) malignancies. The authors believe, and most of us would agree, that in palliative cases, a minimally invasive surgical approach has much to offer the patient in terms of reduced morbidity and mortality and improved quality of life. However, the role of this technology in potentially curative resectional therapy remains controversial.

August 01, 2000

Nucleoside analogs have marked efficacy in indolent lymphoid malignancies, but the tradeoff is the challenge of preventing and treating infections in these patients, according to Susan O’Brien, MD, of M. D. Anderson Cancer Center, Houston. At

August 01, 2000

Laparoscopic procedures have become standard surgical techniques for several benign abdominal diseases. Laparoscopic cholecystectomy, appendectomy, Nissen fundoplication, splenectomy, adrenalectomy, and palliative intestinal bypass procedures are widely accepted as standards of care. It was believed that the success of these laparoscopic procedures would soon transform colorectal surgery for neoplastic diseases. This enthusiasm is evident in many early publications cited in the article by Drs. Wexner and Hwang. The article offers a balanced and thorough review of laparoscopy in the management of colorectal neoplasms and emphasizes the significant controversy surrounding this topic.

August 01, 2000

Laparoscopic surgery for colorectal malignancy is an important topic because of its potential advantages and its oncologic controversies. Drs. Wexner and Hwang have prepared a comprehensive review of the current status of laparoscopic colorectal surgery for malignancy. The relative merits of the new procedure are discussed from a number of perspectives, including the technical aspects of laparoscopic bowel resection, oncologic concerns, and experimental and theoretical effects on tumor growth and host immunity.

August 01, 2000

Three-dimensional (3D) treatment planning refers to the use of software and hardware tools to design and implement more accurate and conformal radiation therapy. This is a major advance in oncology that should lead

August 01, 2000

Laparoscopic colorectal surgery is being utilized increasingly for benign diseases. Recent published series have proven that morbidity and mortality from laparoscopic procedures are superior to those seen after traditional open

August 01, 2000

Three-dimensional (3D) treatment planning refers to the use of software and hardware tools to design and implement more accurate and conformal radiation therapy. This is a major advance in oncology that should lead to

August 01, 2000

Clinical results demonstrate the potential of an investigational drug, exisulind (Aptosyn), to delay the need for androgen-deprivation therapy in men who have undergone prostatectomy and are at risk of prostate cancer recurrence. Detailed

August 01, 2000

Intestinal obstruction in the patient with ovarian cancer is a difficult situation for both patient and physician. In women presenting with ovarian cancer, obstruction is almost never complete.

August 01, 2000

Drs. Randall and Rubin address three subjects important to all patients with advanced-stage epithelial ovarian cancer: (1) the incidence and annual mortality associated with the disease, (2) the use of intestinal surgery at the time of initial surgery, and (3) the use of surgery for intestinal obstruction in patients with recurrent (or progressive) ovarian cancer. I believe that progress in all three areas has been made, albeit slowly.

August 01, 2000

In their excellent review of intestinal obstruction in women with advanced and recurrent ovarian cancer, Drs. Randall and Rubin indicate that median survivals and quality of life for these patients have improved substantially. Data from the International Federation of Obstetrics and Gynecology (FIGO)[1] and the National Cancer Institute’s Survival, Epidemiology, and End Results (SEER) program[2] indicate that the 5-year disease-free survival for advanced-stage disease has risen over the past several decades from approximately 5% to 20%. Therefore, the palliation of intestinal obstruction secondary to metastatic ovarian cancer has become a more urgent issue. The management of recurrent or chronic intestinal obstruction is often complex, and the authors have carefully substantiated issues related to this complication of the malignancy.

August 01, 2000

Chemotherapy is an integral part of treatment for patients with nasopharyngeal carcinoma. Chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease. In

August 01, 2000

Chemotherapy is an integral part of treatment for patients with nasopharyngeal carcinoma. Chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease. In

August 01, 2000

Authors Thomas Randall, MD, and Stephen Rubin, MD, provide a thoughtful, state-of-the-art discussion on current controversies in the management of intestinal obstruction in patients with ovarian cancer.