Platinum-based chemotherapy is commonly used in patients with IC-GCTs. The leading platinum compounds used in cancer chemotherapy are cisplatin, carboplatin and oxaliplatin. They share some structural similarities. However, there are marked differences among them in therapeutic use, pharmacokinetics and adverse effect profiles. Cisplatin is the most highly protein bound, followed by oxaliplatin and carboplatin; the degree of protein binding is related to adverse responses11)
. It appears to be superior to carboplatin in terms of therapeutic effectiveness (germ cell tumors, bladder cancer, and head and neck cancer)12
, however, it has some severe associated toxicity such as ototoxicity and nephrotoxicity.
In 1994, Allen et al.14)
reported the effect of carboplatin in patients with newly diagnosed germinomas of the central nervous system. In 2002, Stern et al.15)
suggested carboplatin could be used to substitute for cisplatin during the treatment of pediatric germ cell tumors and in 2005, You et al.7)
reported results of a cisplatin-based treatment of pediatric patients with IC-GCTs at the Samsung Medical Center and the limitations of cisplatin-based chemotherapy. The EFS rate in the LR group treated with cisplatin-based chemotherapy was 100% and for the HR group it was 88.9%. The EFS rates were similar to the results of current study. However, four of nine patients in the high risk group had hearing difficulty and had a diagnosis of sensorineural hearing loss. In this study, seven patients had pure tone audiometry and speech audiometry by otology experts; none of the patients treated with carboplatin-based chemotherapy had sensorineural hearing loss. And grade 3 or 4 creatinine elevation was not found in patients treated with carboplatin-based chemotherapy, even in HR group patients who received double-dose carboplatin-based chemotherapy. In addition, there was no significant cystitis identified in any of the patients treated with carboplatin-based chemotherapy. And Yoo et al.8)
recommended carboplatin-based chemotherapy in patients with central nervous system-GCTs because many patients may have signs of diabetes insipidus. Cisplatin may not be appropriate for patients with diabetes insipidus because they must be managed by strict input/output measurements along with adequate hydration and desmopressin replacement. Considering the immature renal and hearing function of pediatric patients, carboplatin can be the useful agent for pediatric patients with IC-GCTs.
In contrast to cisplatin, myelotoxicity represents the most prominent adverse effect of carboplatin. Carboplatin induced myelosuppresion is dose-related and results in thrombocytopenia and neutropenia11)
. In this study, the HR group patients received a double-dose carboplatin and needed more frequent RBC and platelet transfusions. The neutrophil recovery was also delayed in HR group patients. Myelosuppression is closely related to infection, which is a major cause of morbidity and mortality in cancer patients16)
. The probability of developing MDI, when a child presents with fever and therapy-induced neutropenia, ranges from 10 to 40%17
. However, cisplatin can also induce myelosuppression and febrile neutropenia. You et al.7)
reported that the frequency of grade 4 neutropenia associated with cisplatin-based chemotherapy was 100% and the frequency of grade 3 or 4 infectious complication was 80% in the LR group, 100% in the HR group. In 2007, Okamoto et al.21)
compared the effects of carboplatin and cisplatin in patients with small cell lung cancer. They reported a high percentage of neutropenia in the carboplatin group (95%) and cisplatin group (90%). However, there was no difference in infection prevalence between the carboplatin group and cisplatin group (P
=0.78). In this study, grade 3 or 4 neutropenia was 100% and grade 3 or 4 febrile neutropenia was 85.7%. In addition, five patients in the HR group had a MDI. However, all infections were controlled by antibiotic treatment and supportive care with no sequelae. No complication or mortality associated with infection occurred in patients treated with carboplatin-based chemotherapy.
In conclusion, carboplatin-based chemotherapy used for the treatment of IC-GCTs is safer and more effective than we expected for the treatment of pediatric patients with IC-GCTs. There was no significant nephrotoxicity and ototoxicity in the patients treated with carboplatin-based chemotherapy. Although hematological toxicities were frequent in the HR group of patients, there were no lethal complications associated with the carboplatin-based treatment. A multicenter prospective, multivariate study is required to determine the long-term efficacy and feasibility of the current protocol.