TY - JOUR
T1 - Dose-intensive chemotherapy in refractory germ cell cancer - A phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation
AU - Nichols, C. R.
AU - Tricot, G.
AU - Williams, S. D.
AU - Van Besien, K.
AU - Loehrer, P. J.
AU - Roth, B. J.
AU - Akard, L.
AU - Hoffman, R.
AU - Goulet, R.
AU - Wolff, S. N.
AU - Giannone, L.
AU - Greer, J.
AU - Einhorn, L. H.
AU - Jansen, J.
PY - 1989
Y1 - 1989
N2 - Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or bearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistent to conventional-dose cisplatin-based therapies.
AB - Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or bearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistent to conventional-dose cisplatin-based therapies.
UR - http://www.scopus.com/inward/record.url?scp=0024338525&partnerID=8YFLogxK
U2 - 10.1200/JCO.1989.7.7.932
DO - 10.1200/JCO.1989.7.7.932
M3 - Article
C2 - 2544687
AN - SCOPUS:0024338525
SN - 0732-183X
VL - 7
SP - 932
EP - 939
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 7
ER -