Sequential Dose-Intensive Paclitaxel, Ifosfamide, Carboplatin, and Etoposide Salvage Therapy for Germ Cell Tumor Patients

Abstract

Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.

Current status and future perspectives in the treatment of advanced testicular cancer

“…[56][57][58][59][60][61][62][63][64][65][66][67][68][69] Paclitaxel was shown to Chemo., chemotherapy; CR, complete response; NED, no evidence of disease; VeIP, vinblastine, ifosfamide, cisplatin; VIP, etoposide (VP-16), ifosfamide, cisplatin. be effective for previously treated testicular cancer because of its unique mechanism of antitumor activity and the premature stabilization of the microtubules assembly, which is different from that of DNAdamaging agents such as cisplatin and ifosfamide.…”

“…The first trial of paclitaxel in pretreated germ cell tumors was undertaken by Motzer et al 56 The effective rate of paclitaxel in the salvage treatment of refractory testicular cancer ranged from 11 to 26% (Table 5). [56][57][58][59][60][61][62][63][64][65][66][67][68][69] More recently, high effective rates (68% and 80%) of a combination chemotherapy with paclitaxel, ifosfamide and cisplatin (TIP) in the treatment of refractory disease were reported by Beyer et al and Motzer et al 60,61 The results reported by Motzer et al showed a high response rate to the TIP regimen in patients with relapsed testicular cancer after conventional dose first-line chemotherapy. 61 Motzer and associates also reported the result of dose-intensive salvage therapy with paclitaxel, ifosfamide, carboplatin and etoposide (PICP) for cisplatin-resistant germ cell tumor patients with unfavorable prognostic features, achieving a 57% CR rate.…”

“…61 Motzer and associates also reported the result of dose-intensive salvage therapy with paclitaxel, ifosfamide, carboplatin and etoposide (PICP) for cisplatin-resistant germ cell tumor patients with unfavorable prognostic features, achieving a 57% CR rate. 62 Paclitaxel-based combination chemotherapy seems to be more effective than high dose chemotherapy for recurrent or cisplatin-resistant germ cell tumors. 61,62 Gemcitabine, a novel pyrimidine anti-metabolite, was proved to be effective in the treatment of cisplatinresistant ovarian germ cell cancer and applied to the treatment of testicular cancer.…”

“…62 Paclitaxel-based combination chemotherapy seems to be more effective than high dose chemotherapy for recurrent or cisplatin-resistant germ cell tumors. 61,62 Gemcitabine, a novel pyrimidine anti-metabolite, was proved to be effective in the treatment of cisplatinresistant ovarian germ cell cancer and applied to the treatment of testicular cancer. 64 Two studies evaluating the efficacy of gemcitabine in heavily pretreated testicular cancer were reported (Table 5).…”

“…Miki and associates found an increased activity of irinotecan hydrochloride in combination with cisplatin or nedaplatin (254-s) according to a basic study using hetero- 51 CBDCA, VP-16, CPA AuBMT 58 18 (31) 23 (40) 12 (21) Broun et al 52 CBDCA, VP-16 AuBMT 25 9 (36) 16 (64) 13 (52) Nakagawa 48 CBDCA, VP-16, IFM PSBCT 16 0 (0) 6 (38) 9 (56) Chemo., chemotherapy; CR, complete response; NED, no evidence of disease; CDDP, cisplatin; VP-16: eptoposide; CPA, cyclophosphamide; IFM, ifosfamide; AuBMT, autologous bone marrow transplantation, PBSCT, peripheral blood stem cell transplantation. 60 paclitaxel, IFM, CDDP 80 9 (11) 45 (56) 54 (68) 20 (27) Motzer et al 61 paclitaxel, IFM, CDDP 30 23 (77) 1 (3) 24 (80) 22 (73) Motzer et al 62 paclitaxel, IFM, CBDCA, VP-16 37 21 (57) 2 (5) 23 (62) 15 (41) 69 CPT-11, CDDP or nedaplatin 14 4 (29) 7 (50) 11 (70) 6 (43) CR, complete response; PR, partial response; NED, no evidence of disease; IFM, ifosfamide; CDDP, cisplatin; CBDCA, carboplatin; VP-16, etoposide; CPT-11, irinotecan hydrochloride.…”