The study showed that the other platinum-based chemotherapy alternatives did not reduce survival and did not significantly increase the incidence of hematological and non-hematological side effects compared with cisplatin-based chemotherapy. To our knowledge, this is the first meta-analysis that examines of the efficacy and side effects of cisplatin versus other platinum chemotherapy in locally advanced NPC.
In the past 20 years, three major advances have significantly improved the prognosis of patients with NPC. First, intensity-modulated radiation therapy can cover the target area and the local expansion area with a good precision. Intensity-modulated radiation therapy can better protect the adjacent normal tissue especially for patients whose tumors extend backward to the cranial nerve [23, 24]. Secondly, the combination of cisplatin-based CCRT, induction chemotherapy, or adjuvant chemotherapy effectively improves the survival rate and disease control of NPC [5, 25–28]. Thirdly, the use of advanced imaging techniques, especially the application of MRI and PET-CT, can better evaluate the local and distant invasion of the tumor, which is very critical for the accurate application of intensity-modulated radiation therapy. However, cisplatin-based chemotherapy regimens are known to increase the acute and late toxicities of radiotherapy . Long-term side effects such as nausea, vomiting, auditory function, renal function or effects on peripheral nerves caused by cisplatin may affect the quality of life of survivors. Moreover, cisplatin-based CCRT requires pretreatment and post-treatment hydration during cisplatin administration to protect the kidneys, which can prolong the hospital stay [14, 16, 17].
Carboplatin, nedaplatin and lobaplatin were successively included in the study as cisplatin substitutes to improve the compliance of patients, reduce the side effects of chemotherapy and meet the clinical needs. A randomized non-inferiority trial showed that there was no difference between carboplatin-based CCRT and cisplatin-based regimen in patients with locally advanced NPC. Moreover, carboplatin showed better tolerance in patients with locally advanced NPC . Two other trials indicated that carboplatin induction chemotherapy combined with CCRT did not improve survival in patients with locally advanced NPC compared with carboplatin induction chemotherapy combined with radiotherapy alone . In addition, carboplatin was less effective than cisplatin when given during CCRT in patients with borderline renal function .
Nedaplatin is a cisplatin analog whose antitumor mechanism and therapeutic effect are similar to that of cisplatin and does not require hydration to protect the kidneys. Two Phase 2 studies have shown that nedaplatin in combination with fluorouracil or docetaxel has an inductive effect on chemotherapy. In addition, nedaplatin-based CCRT is an effective and safe treatment for patients with stage II–IVB NPC, indicating that nedaplatin may be a promising alternative to cisplatin [30, 31]. In a randomized phase III trial, Mai HQ et al.  showed that for patients with stages II–IVB NPC, nedaplatin-based CCRT was not inferior to cisplatin-based CCRT with respect to the 2-year PFS. Subsequent comments  indicate that it is too early to conclude that nedaplatin will replace cisplatin. However, the newly published results of the 5-year follow-up still support the results of the initial report .
Lobaplatin is a third-generation platinum drug. In previous studies, lobaplatin was found to overcome some forms of multiple drug resistance caused by other platinum-based drugs, such as cisplatin or carboplatin . A random non-inferiority trial showed that lobaplatin-based induction chemotherapy plus CCRT has similar survival outcomes and side effects’ profile to cisplatin-based therapy and thus may act a promising alternative . Clinical studies, such as Chictr1900021536, and ChiCTR-IIR-17013112, are still ongoing to further assess the benefits and risks of lobaplatin for NPC and to verify the value of these treatment strategies.
We conducted this meta-analysis to evaluate the efficacy and safety of other platinum-based chemotherapy versus cisplatin-based chemotherapy for locally advanced NPC. Yuan et al.  performed a network meta-analysis on the efficacy of different neoadjuvant chemotherapeutic strategies in the treatment of NPC. The results showed that some cisplatin-based neoadjuvant chemotherapy regimens improved the prognosis of patients with NPC and reduced the toxicity of chemotherapy. However, the optimal neoadjuvant chemotherapy protocol is not fully consistent in terms of survival and efficiency. Horace et al.  showed that the induction chemotherapy regimen, gemcitabine plus cisplatin, shows better performance in terms of survival outcomes. To date, there is no meta-analysis to adequately demonstrate differences in the efficacy of various platinum-based regimens in locally advanced NPC. To reduce bias, we selected RCTs that are clinically registered as eligible studies. Our meta-analysis revealed that there was no significant difference between other platinum-based and cisplatin-based chemotherapy in terms of OS, PFS, DMFS and LRFS. Severe acute hematological side effects (≥ grade 3) such as neutropenia, leukopenia and thrombocytopenia were observed after platinum-based induction chemotherapy or throughout the treatment period, however, such side effects were equivalent to those in the cisplatin treatment group. It is worth noting that risk of anemia was higher in patients receiving other platinum-based treatments. In contrast, the risk of non-hematological side effects such as nausea, vomiting, and weight loss after induction chemotherapy or during the whole treatment period was higher in the cisplatin treatment group. There was no difference in other non-hematological side effects such as xerostomia, dermatitis, mucositis, and elevated levels of aminotransferase between the two groups. Moreover, there was no significant difference in the late side effects such as xerostomia, subcutaneous fibrosis, hearing impairment, trismus, cranial nerve palsy and temporal lobe necrosis between the two groups. The studies included in this meta-analysis did not report any treatment-related disability or death.
The main limitation of this meta-analysis is that some of the studies included were not RCTs, which may affect our research outcomes. Secondly, most studies were conducted in China, which may be a source of potential bias. Third, there are differences in the specific study populations, combined treatment schemes and treatment durations, which may affect further data analyses. Finally, the DNA level of EB virus is a prognostic factor for NPC, however, the included studies could not be analyzed by subgroups.