Cisplatin vs carboplatin: comparative review of therapeutic management in solid malignancies Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Saturday, May 21, 2016

Cisplatin vs carboplatin: comparative review of therapeutic management in solid malignancies



open access:
 Published Online: March 24, 2016

Cisplatin versus carboplatin: comparative review of therapeutic management in solid malignancies - Critical Reviews in Oncology / Hematology 

 Article Outline

Highlights

  • Cisplatin and carboplatin, represent some of the most active cytotoxic agents and are the backbone of most chemotherapeutic regimens.
  • Despite their relative similarities in mechanisms of action, there are significant differences in efficacy and toxicity in various malignancies.
  • Carboplatin is a useful alternative in situations where cisplatin is contraindicated and this is not universally at the expense of efficacy.
  • De novo and acquired platinum resistance is inevitable and understanding the mechanisms of resistance is essential in improving outcomes.

Abstract

The platinum analogues, cisplatin and carboplatin, are among the most widely used chemotherapeutic agents in oncology. Both agents have a broad spectrum of clinical activity in numerous malignancies including gynaecological cancers, germ cell tumours, head and neck cancer, thoracic cancers and bladder cancer. Although the final mechanism of inducing tumour cell apoptosis is similar for both compounds, cisplatin has been shown to be more effective in treating specific tumour types. Whilst more favourable toxicity profiles are often associated with carboplatin, this can frequently translate to inferior response in certain malignancies. This review succinctly collates the evidence for the preferential use of these platinum analogues in particular settings in addition to the long-standing dilemma surrounding the paucity of biomarkers predicting response to these agents.

1. Introduction

Since the serendipitous discovery of the anti-neoplastic activity of cisplatin (cis-diammine-dichloroplatinum(II)) over 30 years ago (Alderden et al., 2006), this agent alongside subsequent analogues (i.e. carboplatin, oxliplatin, satraplatin) has become integral to the gold standard chemotherapeutic management of a myriad of malignancies including gynaecological, germ cell, head and neck, lung and bladder cancers. Cisplatin is the oldest member of this family with a well-recognised toxicity profile including emesis, renal dysfunction, neurotoxicity and ototoxicty. Carboplatin (cis-diammine-cyclobutanedicarboxylato-platinum(II)) was initially believed to have “comparable” therapeutic activity with cisplatin but is associated with significant myelotoxicity (particularly thrombocytopenia) but less nephrotoxicity and neurological sequelae.......


9. Gynaecological cancers

In contrast to most other tumour types reviewed herein, carboplatin-doublets now represent the gold-standard of chemotherapeutic regimens for epithelial ovarian cancer (EOC) in neoadjuvant, adjuvant and palliative settings (Berek et al., 2000). A number of pivotal studies have facilitated the establishment of this treatment paradigm. The largest of these was a non-inferiority phase III Gynaecologic Oncology Group (GOG) study (n = 792) comparing carboplatin-paclitaxel with the then standard combination of cisplatin-paclitaxel for optimally debulked stage III EOC (Ozols et al., 2003). The authors reported equivalent median PFS (20.7 months vs 19.7 months) and OS (57.4 months vs 48.7 months) for carboplatin-paclitaxel and cisplatin-paclitaxel respectively (Ozols et al., 2003). The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75–1.03) and the RR of death was 0.84 (95% CI, 0.70–1.02). Moreover, the carboplatin-doublet was better tolerated with significantly less renal and gastrointestinal toxicities. Although grade 4 leucopenia was more apparent with cisplatin, ≥grade 2 thrombocytopenia was more frequently associated with the carboplatin arm. These observations have been recapitulated in a subsequent European study with superior quality of life associated with carboplatin-paclitaxel without any detriment to survival which was identical to cisplatin-paclitaxel (Greimel et al., 2006). However, in light of the confirmed benefits of intraperitoneal chemotherapy (i.p.) in patients with optimally debulked EOC (Tewari et al., 2015), there has been a renaissance for cisplatin within the adjuvant sphere. For example, the landmark GOG 172 phase III study comparing i.p. vs i.v. cisplatin confirmed a marked improvement in median OS (65.6 months vs 49.7 months) and PFS (23.8 months vs 18.3 months) (Armstrong et al., 2006). The benefit was evident despite a 68% drop-out rate from the i.p. arm which was associated with high rates of grade III/IV toxicities and poor quality of life up to 6 weeks post treatment. Intraperitoneal cisplatin and carboplatin treatment have been compared in a retrospective study as second-line palliative treatment which showed both non-inferiority and similar toxicities (Milczek et al., 2012). With respect to more traditional first line i.v. administration for advanced EOC, a phase III randomised non-inferiority trial published in 2003 comparing the use of cisplatin-paclitaxel and carboplatin-paclitaxel showed a comparable proportion of patients without disease progression at 2 years (40.0% vs 37.5%) and similar PFS and OS rates (Du Bois et al., 2003). Again, the use of carboplatin was shown to be associated with superior tolerability and quality of life (Table 1).

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