Abstract
Gender medicine in the field of oncology is an under-researched area, despite the existing evidence towards gender-dependent response to therapy and treatment-induced adverse effects. Oncological treatment aims to fulfil its main goal of achieving high tumour control by also protecting normal tissue from acute or chronic damage. Chemotherapy is an important component of cancer treatment, with a large number of drugs being currently in clinical use. Cisplatin is one of the most commonly employed chemotherapeutic agents, used either as a sole drug or in combination with other agents. Cisplatin-induced toxicities are well documented, and they include nephrotoxicity, neurotoxicity, gastrointestinal toxicity, ototoxicity, just to name the most frequent ones. Some of these toxicities have short-term sequelae, while others are irreversible. Furthermore, research showed that there is a strong gender-dependent aspect of side effects caused by the administration of cisplatin. While evidence towards sex differences in animal models is substantial, clinical studies considering sex/gender as a variable factor are limited. This work summarises the current knowledge on sex/gender-related side effects induced by platinum compounds and highlights the gaps in research that require more attention to open new therapeutic possibilities and preventative measures to alleviate normal tissue toxicity and increase patients’ quality of life in both males and females.
Highlights
As acknowledged by medical research, the important role of sex and gender in influencing treatment outcome is well recognised in several medical fields, remains poorly investigated in oncology [1]
The aim of the current work is to collate the evidence towards sex/gender-related differences in normal tissue effects induced by platinum compounds, with a specific focus on the most used platinum compound, cisplatin
In a retrospective clinical study reported by Yamamoto et al, a combination between carboplatin and paclitaxel was administered to 227 unresectable stage IIIB-IV non-small-cell lung cancer (NSCLC) patients (147 males and 80 females), showing that in both sexes/genders the response rate reached 39% [57]
Summary
As acknowledged by medical research, the important role of sex and gender in influencing treatment outcome is well recognised in several medical fields, remains poorly investigated in oncology [1] This void must be filled with clinical evidence that should originate from interventional studies and trials evaluating sex/gender-specific dosing regimens to counteract the side effects caused by a variety of chemotherapeutic drugs [1]. The aim of the current work is to collate the evidence towards sex/gender-related differences in normal tissue effects induced by platinum compounds, with a specific focus on the most used platinum compound, cisplatin. Current evidence towards sex/gender-dependent toxicity after cisplatin chemotherapy is primarily based on pre-clinical research, the number of clinical studies exploring this important aspect being limited. In today’s world of personalised medicine, the investigation of gender-specific effects of cancer therapies should be an essential component of clinical trials, which could be tackled without additional costs or deviations from the initial study design
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