High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults

Abstract

Background. A Phase I—II trial to assess the toxicity and efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ cell tumors and metastatic trophoblastic disease was performed. Methods. Thirty‐nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic disease, received tandem high dose therapy combining ifosfamide (7500‐12,500 mg/m2), carboplatin (875‐1225 mg/m2), and etoposide (1000‐1250 mg/m2), followed by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin‐ or carboplatin‐based regimen and the response of 37 could be evaluated; 69 cycles of this tandem high dose therapy were administered. Results. The overall response rate was 46%, including a complete response (CR) rate of 35%. Of 21 patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR. No CRs were obtained in patients with refractory extragonadal germ cell tumors. Nine partial responders after the first cycle became complete responders after the second. Nine (23%) of the patients were long term survivors (> 18 months), 7 of them in continuous CR. Side effects primarily were renal toxicity and entero‐colitis. Seven patients (18%) died of therapy‐related causes. The therapeutic contribution of ifosfamide must be explored and the maximum tolerated doses of this three‐drug regimen remain to be determined. Conclusion. This tandem therapeutic regimen is able to overcome resistance to a platinum‐based regimen in highly refractory germ cell tumors and gestational trophoblastic disease and to cure a number of patients. Cancer 1995; 75:874—85.

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for choriocarcinoma: A case report and literature review

“…However, high-dose ICE exhibited the highest effectiveness among all the regimens the patient had received. Previous reports of high-dose ICE for intractable malignancies reported side effects, such as oral ulcers, esophagitis, nausea and diarrhea, in ~100% of the cases, and liver dysfunction and neurological disorders in ~30% of the cases (8). In terms of myelosuppression, 36% of the patients had infection or sepsis, and 18% succumbed due to severe side effects.…”

“…After excluding male cases or non-gestational choriocarcinoma, our search yielded 21 cases in 11 articles between 1991 and 2013 (Table II) (7,8,(10)(11)(12)(13)(14)(15)(16)(17)(18). Two cases reported by Jean-Pierre Lotz in 1991 (11) were included in the 5 cases reported in 1995 by the same author (8).…”

Salvage high‐dose chemotherapy in patients with germ cell tumors

“…The high treatment-related mortality (17%) that occurred in our patient population before the availability of the colony-stimulating factors was similar to the mortality observed in other series during the same period. [31][32] However, with better patient selection and improved supportive care, the treatment-related mortality that occurred in our experience in the 1990s was 7%, compared with HDCT-related mortality data in GCT patients from the European Bone Marrow Transplantation Solid Tumors Registry. 33 No patient developed myelodysplasia or secondary leukemia after receiving HDCT, even though an increase was reported in other experiences.…”

Long-term results of autologous marrow transplantation for relapsed or refractory male or female germ cell tumors

“…The Table divides the studies based on the number of patients in each study reported to have extragonadal primaries, a prognostic factor known to have a poor outcome for response. 21,22 Several observations may be made from the results described in Table 5. In group A or the three studies that reported 33-45% incidence of extragonadal primaries in their patient pool (A1-A3: Refs 15-18), one or two cycles of HDC (of a two or three-drug regimen) resulted in a 34-45% EFS.…”

“…Patients who were still responsive to induction chemotherapy obtained the most benefit with a 77% eventfree survival at 4 years ( Figure 2, log-rank test, P value 0.0082). Using tandem HDC with ifosfamide/ carboplatin/etoposide and marrow transplantation, Lotz et al 22 showed only an 18% (5/28) long-term disease-free survival (10-84 months) in 28 germ cell tumor patients (18 testis, seven extragonadal, three ovarian) who were all refractory to cisplatin. Other investigators have also indicated the importance of cisplatin-refractoriness as a prognostic factor.…”