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Salvage Chemotherapy with High-Dose Carboplatin Plus Bone Marrow Transplantation (2007) 40, 235–237 & 2007 Nature Publishing Group All rights reserved 0268-3369/07 $30.00 www.nature.com/bmt ORIGINAL ARTICLE Salvage chemotherapy with high-dose carboplatin plus etoposide and autologous peripheral blood stem cell transplant in male pure choriocarcinoma: a retrospective analysis of 13 cases G Papiani1 and LH Einhorn2,3 1Department of Hematology and Oncology, Istituto Oncologico Romagnolo, Ravenna City Hospital, Ravenna, Italy; 2Division of Hematology-Oncology, School of Medicine and Walther Cancer Institute, Indiana University, Indianapolis, IN, USA and 3Lance Amstrong Foundation Professor of Medicine Choriocarcinoma of testes is a very rare tumor with poor Introduction prognosis, usually presenting with high serum level of human chorionic gonadotropin (hCG450 000 mIU/ml) Although germcell tumors(GCTs) account for only 1% of and advanced hematogenous metastases. Data with male malignancies in the United States, it is the most salvage chemotherapy has been sparse, with few long- common malignancy in men aged 20–35 years.1–3 On the term survivors. Between April 1996 and October 2004, basis of histological findings, GCT can be divided in two 184 patients with germ cell tumor were treated at Indiana subgroups: seminoma and nonseminoma. Mixed GCTs University with salvage high-dose chemotherapy (HDCT) account for 30–50% of GCT.4 Choriocarcinoma is seen with autologous peripheral blood stem cell transplant. usually as a small component of mixed GCT in 4–17% of Thirteen had pure choriocarcinoma or choriocarcinoma GCT.5–7 As a pure lesion it is very rare, with a frequency of syndrome (normal testes by palpation and ultrasound, less than 1% of all GCTs.3,5 Choriocarcinoma is defined as normal serum alpha-fetoprotein, advanced hematogenous a GCT composed of two mixed distinct cell population, metastases and high level hCG). All patients had cytotrophoblast and syncytiotrophoblast, which contain progressed following one or two lines of cisplatin high level of human chorionic gonadotropin (hCG).4 combination therapy. HDCT regimen was carboplatin hCG levels above 50 000 mIU/ml are predictive of a 700 mg/m2 and etoposide 750 mg/m2 intravenously given poor prognosis.8–10 Pure choriocarcinoma of the testis is for 3 consecutive days. A second course was given after the most aggressive form of GCT tumor, with a high hematopoietic recovery, usually 3–4 weeks later. The propensity to hematogenous spread at the time of initial median survival was 19 months (range 5–90). Six patients diagnosis. Logothetis11 previously described a choriocarci- (46%) are alive and continuously disease free (cNED) at a noma syndrome. Our definition of choriocarcinoma syn- median follow-up of 37 months (range 19–75). One drome refers to a clinical presentation of patients with additional patient who relapsed after HDCT and was normal testes by palpation and ultrasound, normal serum treated with third line chemotherapy followed by two alpha-fetoprotein, and advanced hematogenous metastases surgical resections of choriocarcinoma is currently alive with high level of hCG. NED at þ 90 months from HDCT. Long-term disease- Metastatic GCTs are curable in 70–80% of cases.1 free survival and potential cure is possible with HDCT in Pure choriocarcinoma of the testis or choriocarcinoma choriocarcinoma patients that progressed after standard syndrome will present usually with serum hCG cisplatin combination therapy. 450 000 mIU/ml and often with pulmonary and nonpul- Bone Marrow Transplantation (2007) 40, 235–237; monary visceral metastases. This accounts for the relatively doi:10.1038/sj.bmt.1705697; published online 11 June 2007 poor prognosis.8 Standard treatment for this tumor follows Keywords: choriocarcinoma; germ cell tumor; high-dose the guidelines for poor-risk nonseminomatous GCTs.12 chemotherapy; salvage treatment; autologous peripheral Patients with serumhCG 450 000 mIU/ml commonly have blood stemcell transplant a plateau in the descent of their hCG with the third and fourth course of initial chemotherapy, and thus it may take several months after completion of chemotherapy before a serologic complete remission (CR) is achieved in patients who were cured with their initial chemotherapy.10 It is difficult to ascertain the cure rate with initial chemotherapy Correspondence: Dr G Papiani, Department of Hematology and for pure choriocarcinoma of testis or choriocarcinoma Oncology, Ravenna City Hospital, Unita` Operativa di Oncologia syndrome, but it is expected to be less than 50%. After Medica, Viale Randi N 5, Ravenna 48100, Italy. E-mail: [email protected] progression, it is unknown whether these patients are Received 8 December 2006; revised 19 March 2007; accepted 21 March curable with salvage chemotherapy. We report a retro- 2007; published online 11 June 2007 spective review of 13 consecutive pure choriocarcinoma or Salvage HDCT in male pure choriocarcinoma G Papiani and LH Einhorn 236 choriocarcinoma syndrome patients treated with salvage high-dose chemotherapy (HDCT). Patients and methods Maintenance oral VP16 partial remission; Between April 1996 and October 2004, 184 germcell ¼ patients were treated with salvage HDCT at Indiana University Hospital.13 Thirteen of these patients had a diagnosis of pure choriocarcinoma of the testis or chorio- carcinoma syndrome. As defined above, patients received Survival months salvage treatment as second- or third-line chemotherapy. mediastinum; PR Before HDCT, all patients had progressed following ¼ standard cisplatin combination therapy. Peripheral HDCT blood stemcells (PBSCs) were collected before HDCT as hCG at reported previously.14 The patients were treated with a HDCT regimen of carboplatin 700 mg/m2 and etoposide 750 mg/m2 intravenously given for 3 consecutive days. The PBSC re-infusion was given on day 0. The second dead of disease; med course of HDCT was given after hematopoietic recovery, ¼ usually 3–4 weeks after the first course. In patients achieving a CR, or normalization of tumor markers, maintenance 2 daily etoposide was given in a dosage of 50 mg/m orally for Sites of metastases at HDCT 21 consecutive days every 4 weeks for three cycles.15 chemotherapy; DOD Results ¼ Platinum refractory We evaluated 13 patients. Patients’ characteristics are depicted in Table 1. The median age was 38 years (range 17–56). Five patients had testis pure choriocarcinoma and eight patients choriocarcinoma syndrome. According to International GermCell Cancer Collaborative Group (IGCCCG), 12 patients had poor prognosis at diagnosis and only one intermediate. Seven patients were platinum No. of prior CT regimens central nervous system; CT refractory (serologic progression within 4 weeks of prior ¼ cisplatin combination therapy when they started HDCT). Ten patients received HDCT as second line and three patients as third line. All patients received two courses of vinblastine, ifosfamide, cisplatin. ¼ HDCT, and six received maintenance daily oral etoposide. IGCCCG class The median survival for the entire 13 patients was 19 months (range 5–90). Six patients (46%) remain alive and continuously disease free (cNED) at þ 19, þ 24, þ 38, currently NED; CNS ¼ 50 000 Poor 1 (BEP) No Lungs 350 +90 curNED Yes 221 000 Poor 1 (BEP) Yes Lungs, bones and liver 8804 +36 cNED Yes þ 39, þ 57 and þ 75, (median follow-up, 37 months). Five hCG at 4 patients achieved cNED status with chemotherapy alone and diagnosis one patient achieved a CR with HDCT followed by surgical excision of teratoma. One additional patient (no. 8; Table 1) achieved a CR with HDCT, but relapsed 27 months later and retroperitoneal nodes; VeIP was treated with third-line chemotherapy followed by two ¼ surgical resections of choriocarcinoma. He is currently alive NED at þ 90 months from initiation of HDCT. Toxicity Toxicity with HDCT has been reported previously.14 continuously disease free; curNED ¼ No toxic deaths occurred in these patients. One patient diagnosis and bones developed acute myelogenous leukemia, at 1 year after HDCT. He had been treated with HDCT as third-line Patients characteristics Age Sites of metastases at chemotherapy and did not receive daily oral etoposide. This patient was treated with allogenic bone marrow transplant, Bleomycin, etoposide, cisplatin; RP and is alive and disease-free of both leukemia and ¼ 16 123 1745 386 Abdominal mass, 44 lungs,7 liver 398 Lung, RP, 24 adrenal9 and Pelvic, liver lungs 56 and med Pelvic 31 RP and 29 lungs 140 Lungs, 000 RP 23 and CNS RP and lungs Abdominal Poor mass and lungs Liver and 24 lungs 000 Poor 83 1 000 (BEP) 231 246 Poor 614 432 Poor 1 (BEP) 4869 400 000 Poor Intermediate Yes Poor 2 (BEP and VeIP) 1 1 (BEP) (BEP) 1 (VeIP) Yes No Lungs and liver 2 (BEP and VeIP) Lungs No Yes No Lungs Yes 5137 Lungs Lungs Lungs +12 and DOD RP Lungs and RP No 5643 1225 4901 +6 DOD +75 cNED 676 +5 DOD 812 13 +36 Yes cNED No +14 DOD +11 No DOD Yes No No PEB choriocarcinoma. Table 1 Patient no. 10111213 38 40Abbreviations: cNED 43 Med, CNS 31 and lungs Lungs, abdominal mass Lungs, RP and CNS Lungs and CNS 990 000 40 793 Poor 477 694 Poor Poor 115 000 Poor 1 (BEP) 2 (BEP and VeIP) 1 (BEP) No 1 (BEP) No Lungs Yes Lungs and Yes RP Lungs Lungs 2700 319 +24 cNED +11 DOD 7000 Yes No 1385 +19 cNED +57 cNED Yes Yes Bone Marrow Transplantation Salvage HDCT in male pure choriocarcinoma G Papiani and LH Einhorn 237 Discussion 4 Cheville J. Classification and pathology of testicular germcell and sex-cord-stromal tumors. Urol Clin North Am 1999; 26: 595–609. Pure coriocarcinoma is a rare cancer and represents less than 5 Mostofi F. Testicular tumors, epidemiologic, etiologic and 1% of GCTs.4,5,7 In a medical review of 10 000 GCT, Ramon pathologic features. Cancer 1973; 32: 1186–1201. et al.17 found 54 cases with an incidence of 0.05%. On gross 6 Mosharafa A, Foster R, Leibovich B, Ulbright T, Bihrle R, et al.
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