Rutgers Robert Wood Johnson University Hospital, Rutgers Cancer Institute of New Jersey
Introduction: Cisplatin is one of the first and most used metal-based chemotherapy agents. It occupies a prominent position in the treatment of urologic neoplasms, especially testicular and bladder cancer. We present a brief biography on the platinum-based agent’s synthesis and implementation into clinical practice.
Methods: A literature review regarding the development and history of cisplatin was conducted.
Results: Cisplatin, or cis-diamminedichloridoplatinum (II), has demonstrated oncologic efficacy in numerous solid cancers, including bladder and testis cancer.
In 1845 Michele Peyrone first synthesized the molecule, a square planar configuration of two ammonia ligands and two chloride ions bonded to a singular platinum atom. Its structure was later described by Alfred Werner in 1893. While its symmetric, elegant architecture became clear – it took several decades to find its ultimate application.
In the 1960s, as enthusiasm for aggressive radical cancer surgeries waned, a renewed effort to advance chemotherapy emerged. Barnett Rosenberg, a biophysicist at Michigan State University, examined interactions between bacterial growth and electric fields. Coincidentally, he used platinum as the experiment’s electrode with ammonium chloride as the buffer solution. He found that his experiment stunted bacterial cellular division. However, the electricity was a bystander. Instead, it was the platinum-based solution, cisplatin, that blocked cell division. The four-armed molecule bound to DNA, cross-linking and distorting it irreparably. He subsequently translated his work to mouse models and similarly noted a robust regression of sarcomas with cisplatin.
In 1973 Dr. Lawrence Einhorn met John Cleland – a young man with metastatic testicular cancer – in Indiana University’s oncology clinic. After minimal response to standard regimens, Einhorn opted to treat Cleland with cisplatin as a last effort. Prior small series had mentioned impressive, but short lived, responses to cisplatin-only systemic therapy. For Cleland, Einhorn modified these regimens and created BVP (bleomycin, vinblastine, and cisplatin) to increase response rate and durability. With dramatic regression of Cleland’s cancer, Einhorn continued his regimen for forty-nine more patients over the next four years, forever altering the systemic treatment paradigm for testicular cancer.
Conclusions: Cisplatin represents a carefully, yet broadly, applied chemotherapy agent. Its serendipitous discovery culminated in FDA approval for use in bladder and testicular cancer in 1978 and remains a mainstay of systematic therapy in many malignancies.
Source of Funding: This work is supported by a grant from the National Cancer Institute (P30CA072720).
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