Salvage combined chemotherapy with paclitaxel, ifosfamide and nedaplatin for patients with advanced germ cell tumors

Abstract

Abbreviations & Acronyms AE = adverse events AFP = alpha-feto protein BEP = bleomycin, etoposide and cisplatin CINV = chemotherapy-induced nausea and vomiting CR = complete response GCT = germ cell tumor HCG = human chorionic gonadotropin HDCT = high-dose chemotherapy IGCCCG = International Germ Cell Cancer Collaborative Group LN = lymph node NED = no evidence of disease NC = no change of visible disease NCm-= no change of visible disease with serum tumor marker normalization NCm+ = no change of visible disease without serum tumor marker normalization OS = overall survival PD = progressive disease PFS = progression-free survival PR = partial response PRm-= partial response with marker normalization PRm+ = partial response without marker normalization PTX = paclitaxel RPLND = retroperitoneal lymph node dissection STM = serum tumor marker TIN = paclitaxel, ifosfamide and nedaplatin TIP = paclitaxel, ifosfamide and cisplatin TRD = treatment-related deaths VeIP = vinblastine, ifosfamide and cisplatin VIP = etoposide, ifosfamide and cisplatin Objectives: To investigate the efficacy of combined regimen with paclitaxel, ifosfamide and nedaplatin as salvage chemotherapy in patients with cisplatin-refractory or multiple relapsed germ cell tumors. Methods: A total of 65 patients refractory to cisplatin-based chemotherapy or with relapse after induction or salvage chemotherapy received paclitaxel 210 mg/m 2 on day 1, ifosfamide 1.2 g/m 2 on days 2-6 and nedaplatin 100 mg/m 2 on day 2 of a 3-week cycle. The primary and secondary end-points were the response rate and overall survival, respectively. Results: Paclitaxel, ifosfamide and nedaplatin therapy was carried out as second-line therapy in 17 patients, third-line in 31 and fourth-line or later in 17. Patients were pretreated with a median of six cycles of platinum-based chemotherapy (range 3-15 cycles). The overall response rate was 62.9%, including one patient with complete response and 38 with partial response. Serum tumor marker levels normalized in 35 (56.5%) patients. Overall survival at a median follow up of 34 months was 59.3%, and median time to progression was 12 months. Multivariate analysis showed that serum tumor marker normalization was the only independent predictor of better progression-free survival and overall survival. Grade 3/4 of neutropenia, anemia and thrombocytopenia was observed in 96.9%, in 81.5%, and in 90.8% of patients, respectively. Conclusion: Paclitaxel, ifosfamide and nedaplatin chemotherapy appears to be effective when used as first or second salvage treatment in advanced relapsed germ cell tumors. Even after fourth-line therapy, patients with serum tumor marker normalization might have a chance for a cure.

Irinotecan and nedaplatin as salvage therapy for patients with advanced germ cell tumors following intensive treatment with cisplatin-based combination chemotherapies

“…For example, Nicolai et al [20] applied a combination regimen with paclitaxel, cisplatin and gemcitabine as third-line or even later salvage chemotherapy, and achieved a response rate of 36.4 % and long-term survival of 18.2 % with no evidence of disease. Nakamura et al [21] also reported further favorable outcomes of a combined regimen with paclitaxel, ifosfamide and nedaplatin, showing an overall response rate of 62.9 % and OS rate of 59.3 % at a median follow-up of 34 months. Considering these findings, it would be an interesting approach to combine an additional agent with IN therapy to further improve long-term disease control in patients with intractable GCTs.…”

“…Considering the intensive treatment history with TIP prior to the initiation of IN in all patients included in this series, the impact of salvage IN therapy on the long-term disease control in patients with intractable GCTs might be acceptable. However, several recent studies using regimens different from that combining irinotecan and a platinum agent have also shown favorable oncological outcomes as salvage chemotherapies for advanced GCTs [20][21][22]. For example, Nicolai et al [20] applied a combination regimen with paclitaxel, cisplatin and gemcitabine as third-line or even later salvage chemotherapy, and achieved a response rate of 36.4 % and long-term survival of 18.2 % with no evidence of disease.…”

Organic effects of associating paclitaxel with a lipid-based nanoparticle system on a nonhuman primate, <em>Cebus apella</em>

“…19 These data are in agreement with the literature, since the main adverse effects observed in treatment with commercial PTX are the following: adverse reactions relating to the bone marrow (alterations in leucocytes, thrombocytopenia, anemia induced by direct damage to erythrocytes), infections, hypersensitivity to hemorrhage, and neurotoxicity. 35,40,41 In relation to biochemical parameters, no relationship between PTX dose and alterations in hepatic function was demonstrated in patients without base hepatic alterations. Published research showed only rare relationships to hepatic necrosis and hepatic encephalopathy.…”

“…33 Data from the analysis of erythrogram of groups treated with commercial PTX indicated a possible medicationinduced anemia and a discrete anisocytosis related to the decline of the animals' health due to drug action. [34][35][36] In the leukocyte series of animals treated with LDE-PTX, the percentage of neutrophils suffered a decline compared with NC group; however, they were above the acceptable minimum for this species. This differed from the data observed in animals treated with commercial PTX, in which there was a significant decline in the absolute number of neutrophils.…”

Less nephrotoxicity of paclitaxel and ifosfamide plus nedaplatin for refractory or relapsed germ cell tumors in patients with impaired renal function

“…For GCTs, nedaplatin monotherapy has an objective response rate of 80%, with six CRs and six PRs, as first‐line therapy . As combination chemotherapy with nedaplatin instead of cisplatin, several regimens have been tested, and they showed a similar antitumor effect to cisplatin‐based regimens with tolerable toxicities …”