Salvage chemotherapy with paclitaxel and gemcitabine plus nedaplatin (TGN) as part of multidisciplinary therapy in patients with heavily pretreated cisplatin-refractory germ cell tumors.
BACKGROUND
We investigated the efficacy and toxicity of a regimen consisting of paclitaxel and gemcitabine plus nedaplatin, a derivative of cisplatin (TGN) in patients with heavily pretreated cisplatin-refractory germ cell tumors (GCTs).


METHODS
Fifteen patients with advanced GCTs were treated with the TGN regimen. The combination chemotherapy consisted of paclitaxel (210 mg/m(2)) on day 1 and gemcitabine (1000 mg/m(2)) on days 1 and 8 in combination with nedaplatin (100 mg/m(2)) on day 2 every 3 weeks.


RESULTS
Patients enrolled in this study had been heavily pretreated with a median of 12 platinum-containing cycles (range, 7 to 26 cycles). Most of the regimens had included paclitaxel and ifosfamide plus cisplatin or nedaplatin (TIP/TIN) chemotherapy. The median follow-up period of the present study was 15 months. Patients received 2-11 cycles of the TGN combination chemotherapy. Six patients received the treatment combined with other therapeutic modalities; 2 patients received radiation therapy for retroperitoneal lymph node metastasis, 1 patient had cyber-knife radiosurgery for brain metastasis and 3 patients had radiofrequency ablation for liver and lung metastasis. Seven (46.7%) of the 15 patients achieved an objective response; 6 had marker-negative partial responses (PRs) and 1 had a marker-positive PR. Two (13%) of the 7 patients with PRs achieved a disease-free status after chemotherapy combined with RT and followed by surgical resection. However, 10 patients died of the disease and 3 patients are still alive with the disease.


CONCLUSIONS
The TGN regimen alone had limited efficacy in this patient population, with severe but manageable toxicities. However, TGN chemotherapy may offer a chance of cure for some heavily pretreated cisplatin-refractory (TIP/TIN-refractory) patients as part of multidisciplinary therapy.
Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
Takumi
T
Shiraishi
Terukazu
T
Nakamura
Kazuya
K
Mikami
Natsuki
N
Takaha
Akihiro
A
Kawauchi
Tsuneharu
T
Miki
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary / Q000601:surgery; D017115:Catheter Ablation; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery; D008175:Lung Neoplasms / Q000556:secondary / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D016634:Radiosurgery; D018714:Radiotherapy, Adjuvant; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000093542:Gemcitabine
D009944:Organoplatinum Compounds; D003841:Deoxycytidine; C053989:nedaplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine