Docetaxel (Taxotere) in combination: a step forward. 1995

H A Burris, and S Fields, and N Peacock
Hematology/Oncology Service Drug Development Program, Brooke Army Medical Center, Ft Sam Houston, TX, USA.

Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is a hemisynthetic derivative from European yew that inhibits tubulin depolymerization and enhances the formation of microtubule bundle aggregates, causing cell death. Activity against a variety of tumor types has been reported. Single-agent chemotherapy is rarely curative; hence, combination regimens are the logical next step in the attempt to improve tumor reduction and prolong survival. In preclinical studies, docetaxel has shown synergism with vinorelbine (Navelbine; Burroughs Wellcome Company, Research Triangle Park, NC), etoposide, cyclophosphamide, 5-fluorouracil, and methotrexate against a variety of murine tumors; in each case, at least 60% of the maximum tolerated dose could be administered without additional toxicity. Similar studies indicated an overlap in dose-limiting toxicity for docetaxel with cisplatin or doxorubicin, whereas with vincristine at least 80% of the maximum tolerated dose could be administered without additional toxicity. A number of docetaxel combinations are currently undergoing clinical evaluation and preliminary results appear to be encouraging. In a phase I trial, the docetaxel/5-fluorouracil combination exhibited activity against refractory solid tumors; grade IV neutropenia was observed, but there was no increase in gastrointestinal toxicity. The docetaxel/doxorubicin combination demonstrated impressive antitumor activity as front-line therapy for metastatic breast cancer (response rate, 70%), with little evidence of mucositis and dose-limiting toxicity experienced by only a minority of patients. Among 12 heavily pretreated phase I patients, the docetaxel/cyclophosphamide combination produced two partial responses in patients with breast cancer; three patients had febrile neutropenia and two had grade II mucositis. The docetaxel/vinorelbine combination produced responses at all dose levels as front-line therapy for metastatic breast cancer; dose-limiting toxicity was experienced by two patients, but only when the vinorelbine dose was raised to 22.5 mg/m2. In phase II studies in non-small cell lung cancer, preliminary results have shown the docetaxel/cisplatin combination to have a promising level of activity and an acceptable toxicity profile. Future trials will continue to evaluate the role of docetaxel in combination and in sequential regimens, most particularly in metastatic breast cancer and non-small cell lung cancer.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D001943 Breast Neoplasms Tumors or cancer of the human BREAST. Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077143 Docetaxel A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER. Docetaxel Anhydrous,Docetaxel Hydrate,Docetaxel Trihydrate,Docetaxol,N-Debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol,NSC 628503,RP 56976,RP-56976,Taxoltere Metro,Taxotere,N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxol,RP56976
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000369 Aged, 80 and over Persons 80 years of age and older. Oldest Old

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