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Bending the Curve Trial by Trial
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Topoisomerase inhibitorsUsed in a few countriesDerivative of an earlier drugNeeds review

Belotecan

Also known as CKD-602, Camtobell

A water-soluble camptothecin analogue developed by Chong Kun Dang Pharmaceutical of Seoul and given by intravenous infusion. Randomised phase 2b and phase 3 trials have compared it with topotecan or etoposide in small cell lung cancer and ovarian cancer.

From discovery to approval

  1. 1998 · Earliest report found

    A 1998 paper reports CKD602, a novel water-soluble camptothecin analogue, as a nanomolar inhibitor of topoisomerase I with activity against human tumour xenografts. A 2003 profile says Chong Kun Dang was developing it and that phase II trials were underway by August 2000.[2][3][1]

  2. No approval is recorded on this site.

How it works

A 2021 trial report describes it as a semi-synthetic camptothecin analogue with a water-solubilising group at position 7, which blocks topoisomerase I so that single-strand DNA breaks are not religated, disrupting DNA replication and inducing apoptosis.[1]

Where it came from and why

The 1998 paper concludes that CKD602 warrants clinical investigation as a potent topoisomerase I inhibitor, and reports a therapeutic margin four times higher than topotecan's. The papers cited do not state the original aim in more detail.

Cancers

  • Small cell lung cancer

    In a randomised phase 2b study of 164 patients with sensitive-relapsed disease, belotecan and topotecan had response rates of 33% and 21% (P=0.09), and median overall survival was 13.2 against 8.2 months (HR 0.69, 95% CI 0.48 to 0.99).[4]

  • Ovarian cancer

    In a randomised phase 2b study of 140 patients with recurrent ovarian cancer, response rates were 29.6% with belotecan and 26.1% with topotecan; overall survival favoured belotecan in the per-protocol population (39.7 against 26.6 months, P=0.034).[1]

Family and partners

Derived from: Camptothecin

Worth knowing

  • In a retrospective single-centre series of 63 patients with recurrent or refractory epithelial ovarian cancer, the overall response rate to belotecan was 30.2%, including 9 complete remissions.[5]
  • In the phase III trial of 147 patients with extensive-stage small cell lung cancer, the response rate was 59.2% with belotecan plus cisplatin and 46.1% with etoposide plus cisplatin, and grade 3 and 4 anaemia and thrombocytopenia were more frequent with belotecan; no significant difference in overall or progression-free survival was seen.[6]

References

  1. Kim HS, Park SY, Park CY, Kim YT, Kim BJ, Song YJ, et al. A multicentre, randomised, open-label, parallel-group Phase 2b study of belotecan versus topotecan for recurrent ovarian cancer. Br J Cancer. 2021;124(2):375-382. PubMedDOI
  2. Lee JH, Lee JM, Kim JK, Ahn SK, Lee SJ, Kim MY, et al. Antitumor activity of 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitor. Arch Pharm Res. 1998;21(5):581-90. PubMedDOI
  3. Crul M. CKD-602. Chong Kun Dang. Curr Opin Investig Drugs. 2003;4(12):1455-9. PubMed
  4. Kang JH, Lee KH, Kim DW, Kim SW, Kim HR, Kim JH, et al. A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer. Br J Cancer. 2021;124(4):713-720. PubMedDOI
  5. Kim YM, Lee SW, Kim DY, Kim JH, Nam JH, Kim YT. The efficacy and toxicity of belotecan (CKD-602), a camptothericin analogue topoisomerase I inhibitor, in patients with recurrent or refractory epithelial ovarian cancer. J Chemother. 2010;22(3):197-200. PubMedDOI
  6. Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, et al. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016;16(1):690. PubMedDOI
  7. Lee DH, Kim SW, Suh C, Lee JS, Lee JH, Lee SJ, et al. Belotecan, new camptothecin analogue, is active in patients with small-cell lung cancer: results of a multicenter early phase II study. Ann Oncol. 2008;19(1):123-7. PubMedDOI