Topotecan as second-line therapy for ovarian cancer: dosage versus toxicity. 2005

Maurie Markman
University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. mmarkman@mdanderson.org

In this issue of The Oncologist, Armstrong et al. present an analysis of the use of topotecan (Hycamtin; GlaxoSmithKline, Philadelphia, http://www.gsk.com) in the second-line treatment of both ovarian cancer and small cell carcinoma of the lung. This cytotoxic agent has clearly been demonstrated to be a useful drug in a population of patients with both of these conditions. However, the description of the nature of the toxicity, as stated in the manuscript, must be questioned along with comments made regarding the relative toxicity of alternative cytotoxic agents frequently used in similar settings. The purpose of this discussion absolutely is not to negate the unquestioned, demonstrated usefulness of topotecan as second-line therapy in ovarian cancer but rather to point out that the U.S. Food and Drug Administration-approved dose level of 1.5 mg/m(2) per day x 5 days can cause substantial and highly clinically relevant bone marrow toxicity. Whether this toxicity, which can result in a level of fatigue that may cause responding patients to discontinue treatment, should simply be labeled "excessive" rather than "cumulative" appears to be a matter of semantics rather than an important distinction. Whether delivery of a lower dose of topotecan (1 mg/m(2)-1.25 mg/m(2) per day x 5 days) will essentially eliminate concern for the development of severe clinically relevant marrow toxicity is uncertain, but the risk will certainly be substantially reduced.

UI MeSH Term Description Entries
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D001853 Bone Marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Marrow,Red Marrow,Yellow Marrow,Marrow, Bone,Marrow, Red,Marrow, Yellow
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D017322 Clinical Trials, Phase II as Topic Works about studies that are usually controlled to assess the effectiveness and dosage (if appropriate) of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques. These studies are performed on several hundred volunteers, including a limited number of patients with the target disease or disorder, and last about two years. This concept includes phase II studies conducted in both the U.S. and in other countries. Drug Evaluation, FDA Phase 2 as Topic,Drug Evaluation, FDA Phase II as Topic,Evaluation Studies, FDA Phase 2 as Topic,Evaluation Studies, FDA Phase II as Topic
D017326 Clinical Trials, Phase III as Topic Works about comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries. Clinical Trials, Phase 3 as Topic,Drug Evaluation, FDA Phase 3 as Topic,Drug Evaluation, FDA Phase III as Topic,Evaluation Studies, FDA Phase 3 as Topic,Evaluation Studies, FDA Phase III as Topic
D019772 Topotecan An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I. 9-Dimethylaminomethyl-10-hydroxycamptothecin,Hycamtamine,Hycamtin,NSC-609699,Nogitecan Hydrochloride,SK&F-104864-A,SKF-104864-A,Topotecan Hydrochloride,Topotecan Monohydrochloride, (S)-Isomer,9 Dimethylaminomethyl 10 hydroxycamptothecin,Hydrochloride, Nogitecan,Hydrochloride, Topotecan,NSC 609699,NSC609699,SK&F 104864 A,SK&F104864A,SKF 104864 A,SKF104864A

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