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
- 1. Introduction
- 2. Non-small cell lung cancer (NSCLC)
- 3. Small-cell lung cancer (SCLC)
- 4. Malignant mesothelioma
- 5. Oesophageal and gastric cancer
- 6. Germ cell tumours
- 7. Bladder cancer
- 8. Cancer of unknown primary (CUP)
- 9. Gynaecological cancers
- 10. Head and neck cancers
- 11. Conclusions
- Conflict of interest
- References
- Biography
Highlights
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).
