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FDA Approved Drugs » 2007
Medical Areas: Oncology | Family Medicine

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Hycamtin (topotecan hydrochloride)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: GlaxoSmithKline
Approval Status: Approved October 2007
Treatment Area: small cell lung cancer

General Information

Hycamtin (topotecan) is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks.

Hycamtin is specifically indicated for the treatment of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.

Hycamtin is supplied as a 0.25 mg and 1 mg capsule designed for oral administration. The recommended initial dose of the drug is 2.3 mg/m2/day once daily for 5 consecutive days, repeated every 21 days. The calculated oral daily dose should be rounded to the nearest 0.25 mg, and the minimum number of 1 mg and 0.25 mg capsules should be prescribed. The same number of capsules should be prescribed for each of the 5 dosing days.

Clinical Results

FDA Approval
FDA approval of Hycamtin was based on the results of a clinical trial. This randomized, comparative, open label study enrolled 115 subjects who were prior responders (complete or partial) to firstline chemotherapy, were not considered candidates for standard intravenous chemotherapy, and had relapsed at least 45 days from the end of first-line chemotherapy. The subjects received Hycamtin (2.3 mg/m2/day administered for 5 consecutive days repeated every 21 days) and Best Supportive Care (BSC) or BSC alone. The primary endpoint was overall survival. Median survival in the Hycamtin arm was 25.9 weeks (95% CI, 18.3 to 31.6) versus 13.9 weeks (95% CI, 11.1 to 18.6) in the BSC alone arm (log-rank P = .0104).

Side Effects

The side effects associated with the use of Hycamtin may include, but are not limited to, the following:

  • Anemia
  • Leukopenia
  • Neutropenia
  • Thrombocytopenia
  • Nausea
  • Vomiting
  • Diarrhea

Mechanism of Action

Hycamtin (topotecan) is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. The cytotoxicity of topotecan is thought to be due to double strand DNA damage produced during DNA synthesis, when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA. Mammalian cells cannot efficiently repair these double strand breaks.

Literature References

Shah C, Ready N, Perry M, Kirshner J, Gajra A, Neuman N, Garziano S A multi-center phase II study of weekly topotecan as second-line therapy for small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 2007 Jul;57(1):84-8

Choi HJ, Cho BC, Shin SJ, Cheon SH, Jung JY, Chang J, Kim SK, Sohn JH, Kim JH Combination of topotecan and etoposide as a salvage treatment for patients with recurrent small cell lung cancer following irinotecan and platinum first-line chemotherapy. Cancer chemotherapy and pharmacology 2007 Jun 19

Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2007 May 20;25(15):2086-92.

Garst J, Herndon JE 2nd, Shafman T, Campagna L, Blackwell S, Padilla K, Bjurstrom T, Andrews C, Maravich-May D, Anderson E, Crawford J A phase I study of dose-dense topotecan given upfront to standard therapy in patients with small cell lung cancer. Clinical drug investigation 2006;26(5):257-66

O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2006 Dec 1;24(34):5441-7

Additional Information

For additional information regarding Hycamtin or small cell lung cancer, please visit the Hycamtin web page.