Assessment of amifostine as protection from chemotherapy-induced toxicities after conventional-dose and high-dose chemotherapy in patients with germ cell tumor.
BACKGROUND
We assessed the efficacy of amifostine for protection from chemotherapy-induced toxicities in patients treated with conventional-dose paclitaxel, ifosfamide, cisplatin (TIP) and high-dose carboplatin, etoposide and thiotepa (CET) followed by peripheral blood progenitor cell (PBPC) rescue.


METHODS
In a prospective single-center study 40 patients with relapsed or refractory germ-cell tumors (GCT) were treated with 3 cycles of conventional-dose TIP followed by one cycle of high-dose CET. Patients were randomized either to receive one fixed dose of 500 mg amifostine per day of conventional-dose TIP and two fixed doses of 500 mg per day amifostine during high-dose CET (group A, n = 20) or no amifostine (group B, n = 20). Prior to the first cycle of TIP, one course of 175 mg/m2 paclitaxel and 5 g/m2 ifosfamide (TI) followed by granulocyte-colony stimulating factor (G-CSF) at 10 microg/kg/day were given for PBPC mobilization.


RESULTS
Toxicities and response to conventional-dose TIP and high-dose CET could be evaluated in 40 patients (100%) and 32 of 40 patients (80%), respectively. Peripheral neurotoxicity (i.e. paresthesia or sensorymotor impairment), hearing impairment, hematologic toxicity, nephrotoxicity, nausea, myalgia, skin- and liver-toxicity did not differ siginificantly between the two patient groups. Likewise, the response rates to TIP and high-dose CET were comparable in patients with or without amifostine. After a median follow-up of 18 months, 8 of 20 (40%) patients of group A and 6 of 20 (30%) patients of group B are without relapse.


CONCLUSIONS
Repeated low doses of 500 mg amifostine additional to conventional-dose TIP or high-dose CET showed no unequivocal advantage in protection from treatment-related toxicities. Furthermore, no significant differences in response rates or survival could be observed in this small number of patients.
Rick
O
O
Klinik für Innere Medizin m. S. Hämatologie/Onkologie, Universitatsklinikum Charité, Humboldt Universität, Berlin, Germany. oliver.rick@charite.de
Beyer
J
J
Schwella
N
N
Schubart
H
H
Schleicher
J
J
Siegert
W
W
D000328:Adult; D004999:Amifostine / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D043823:Taxoids
D011837:Radiation-Protective Agents; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D004999:Amifostine; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide