1. Nephrotoxicity of heptaplatin: a randomized comparison with cisplatin in advanced gastric cancer
Jin-Hee Ahn, Yoon-Koo Kang, Tae-Won Kim. Cancer Chemother Pharmacol(2002) 50: 104–110
Heptaplatin, cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II) (SKI-2053R, Sunpla) is a recently developed platinum derivative. In vitro studies have shown this new analogue to have high antitumor activity against various cancer cell lines, including cisplatin-resistant cancer cell lines. A preclinical study has also indicated that heptaplatin has a favorable toxicity proﬁle in general pharmacological evaluation and that it might produce less nephrotoxicity than cisplatin. In a phase I clinical trial all three patients who received a dose of 480 mg/m2 heptaplatin developed severe nephrotoxicity (grade 2 azotemia and proteinuria), and the maximal tolerated dose was determined to be 480 mg/m2. A phase II study also demonstrated that this agent is active in the treatment of patients with advance gastric cancer (AGC) and has a favorable toxicity proﬁle. In that study, the most common nonhematological toxicity was proteinuria (grade 1 or 2) seen in 80% of patients, but it was concluded that the proteinuria was mild and reversible.
2. Platinum‑based drugs: past, present and future
Shahana Dilruba • Ganna V. Kalayda. Cancer Chemother Pharmacol (2016) 77:1103–1124
Among other third-generation drugs, lobaplatin and heptaplatin received only regional approval. Lobaplatin (Fig. 1) is approved in China for the therapy of metastatic breast cancer, chronic myelogenous leukemia and SCLC. Its dose-limiting toxicity is thrombocytopenia. Heptaplatin (Fig. 1) has a bulkier amine ligand but is structurally similar to lobaplatin. The drug was demonstrated to be stable in solution, to have no remarkable toxicity and to retain cytotoxic activity in cisplatin-resistant cell lines. Heptaplatin is currently applied in the Republic of Korea for the treatment of gastric cancer. A Phase III study showed that heptaplatin combination with 5-luorouracil is comparable to cisplatin/5-luorouracil regimen with less severe hematological side effects.