High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation for male germ cell tumor. Preliminary report

AIM: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7-15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The aim of this study was to investigate the efficacy and safety of high-dose chemotherapy (HDCT) for the treatment of patients with advanced testicular cancer. METHODS: Fourteen patients were treated with high-dose carboplatin, etoposide and cyclophosphamide (with or without THP-adriamycin) followed by peripheral blood stem cell transplantation. The treatment was used for two refractory cases, a second relapse, and for consolidation after the first relapse in one case each. It was also used for nine cases as part of the first-line treatment following primary conventional-dose chemotherapy, and for one case as the first salvage for a late recurrent tumor of teratoma with malignant transformation. RESULTS: The first two patients who received intensive pretreatment with cisplatin-based chemotherapy did not respond to HDCT. The two patients who were treated with HDCT as the first or second salvage therapy achieved successful outcomes. The results for the subsequent nine patients (consisting of two with stage IIIC, five with IIIB2, one with IIB, and one extragonadal seminoma) were two progressive disease, three no change and four partial remission. Only three are alive with NED following salvage surgery. Finally, a case of teratoma with malignant transformation did not respond well to two cycles of HDCT. There were no marked adverse reactions except one episode of severe neutropenic colitis. CONCLUSIONS: The results demonstrated the limited efficacy of HDCT even in cases with a good to intermediate risk rating according to classification by the International Germ Cell Cancer Collaborative Group. Because treatment for relapse after HDCT is extremely difficult, new HDCT regimens consisting of drugs that are not used in induction chemotherapy need to be established.     

Clinical study of high-dose chemotherapy with peripheral blood stem cell transplantation for poor-risk germ cell tumor

Between January 1997 and December 1998, six patients with germ cell tumor were treated with high-dose CEC: carboplatin (1,500 mg/m2), etoposide (1,200 mg/m2) and cyclophosphamide (100 mg/kg), followed by peripheral blood stem cell transplantation (PBSCT) at Nagoya University Hospital. Four patients received one cycle of high-dose CEC and two received two cycles. The reasons why the high-dose CEC was administered included: 1) refractory to the induction chemotherapy (AFP/beta-HCG elevated during the induction chemotherapy or prolonged half-life of each marker) in three patients, 2) relapse in two patients, and 3) consolidation in one with unresectable mediastinal residual tumor. There were no treatment-related deaths and grade 1 hepatotoxicity occurred in one (17%) patient. The median duration (range) from PBSCT until a granulocyte count of 500/microL and a platelet count of 50,000/microL was 8.5 (8-11) and 11 (9-16) days, respectively. Of the six patients studied, 5 responded to the treatment; two achieved a complete response (CR) and three achieved a partial response (PR). One patient achieving a CR and two achieving a PR remained in complete remission after 23 to 24 months of follow-up, while the remaining patients with a CR, a PR and an incomplete response died of the disease. High-dose CEC could be administered without serious toxicity but the effectiveness of high-dose CEC for the poor-risk patients with germ cell tumor needs to be further investigated.     

High-dose chemotherapy for male germ cell tumor

Today, 20-30% of male patients with advanced germ cell tumor (GCT) do not have durable, complete remission in spite of cis-platinum (CDDP)-based chemotherapy. High-dose chemotherapy (HDCT) has been tried in CDDP refractory GCT patients. Initially HDCT was performed with autologous bone marrow transplantation in heavily treated patients. However, the clinical outcome was not good and the treatment-related death rate was not ignorable. Therefore, earlier introduction of HDCT with peripheral blood stem cell transplantation was preferable as it renders HDCT more effective and less toxic, and multicycle HDCT is feasible. The durable free rate of recent HDCT for refractory GCT patients is 32-65%. HDCT is also performed as first line chemotherapy for poor prognosis GCT patients. Induction chemotherapy followed by multicycles of HDCT was tried. The durable free rate of recent HDCT as first line chemotherapy is 43-73%. Although previous reports suggest the superiority of HDCT, one recent randomized controlled trial (RCT) failed to show an improvement with one cycle of HDCT followed by three cycles of standard-dose chemotherapy (SDCT) compared with four cycles of SDCT. Ongoing RCT comparing multicycles of HDCT with SDCT for poor prognostic GCT patients will clarify the role of HDCT. Recently, new regimens of HDCT containing paclitaxel have been devised. In this review, the history, current status and future of HDCT for advanced or refractory GCT will be discussed.     

Retroperitoneal extragonadal germ cell tumor presenting as a bulky pelvic mass of the obturator fossa

Extragonadal germ cell tumors (EGGCT) are commonly found in the midline of the body. We report a rare case of a retroperitoneal EGGCT presenting as a bulky pelvic mass located between the left internal and external iliac arteries in a 29-year-old man. His alpha-fetoprotein level was 12946.2 ng/mL and the biopsy of the tumor revealed a nonseminomatous germ cell tumor. After three cycles of chemotherapy (bleomycin/etoposide/cisplatin) followed by resection of all residual tumors, one cycle of salvage chemotherapy (etoposide/ifosphamide/cisplatin) was added. The patient was disease free at 21-month follow up.     

Treatment of patients with poor prognosis anaplastic germ cell tumours (AGCT) of the testis and other sites

Between 1977 and 1986, 170 male patients with anaplastic germ cell tumours (AGCT) completed chemotherapy with POMB/ACE (platinum, vincristine (oncovin), methotrexate, bleomycin, actinomycin D, cyclophosphamide and etoposide). By increasing the number of courses of POMB in 1979 we have been able to compensate for adverse prognostic factors. Since then each patient has received a minimum of three courses of POMB and 139 patients have completed therapy with an overall survival of 89%, and for those patients who had not received prior radiotherapy the survival is 92%. By increasing the number of courses of POMB, the initial serum concentrations of human chorionic gonadotrophin (hCG greater than 50,000 IU/I) and/or alpha-fetoprotein (AFP greater than 500 kU/l) have ceased to be poor prognostic variables. Neither stage at presentation nor the volume of metastatic disease is a major adverse prognostic variable using this chemotherapy.     

Cumulative prior dose of cisplatin as a cause of the nephrotoxicity of high-dose chemotherapy followed by autologous stem-cell transplantation.

BACKGROUND: Nephrotoxicity is one of the most frequent dose-limiting factors of high-dose chemotherapy to create tolerance of autologous peripheral blood stem-cell transplantation (PBSCT) for the treatment of malignant diseases. The relative importance of factors that may be responsible for the development of nephrotoxicity varied in different trials. METHODS: The factors affecting nephrotoxicity in the early period of high-dose ifosfamide, carboplatin and etoposide treatment (ICE) followed by autologous PBSCT was investigated in 47 patients. ICE was given as a conditioning regimen for 6 days. Nephrotoxicity was defined as an increase in the serum creatinine concentration of 0.5 mg/dl or more over individual baseline levels. RESULTS: Eleven patients developed nephrotoxicity (23.4%). There was no significant difference in baseline renal function between patients with nephrotoxicity and those without. No differences were found between the two groups in terms of average total doses of ICE, infections and antibiotic use. The age of patients was higher in those with nephrotoxicity (37+/-3.7 vs 26+/-1.7 years, P=0.019). The cumulative cisplatin dose administered prior to this regimen was higher in the group that developed nephrotoxicity (470 vs 227 mg/m(2), P=0.02). The overall mortality rate was 17%, but the transplant-related deaths were higher in the presence of nephrotoxicity (54.5 vs 5.5%, P=0.001). CONCLUSIONS: The cumulative dose of cisplatin is a strong risk factor for the development of nephrotoxicity in patients who receive high doses of ICE followed by PBSCT. Nephrotoxicity may occur with much lower doses than the currently recommended maximum doses.     

Preliminary observations for a new treatment in children with primary intracranial yolk sac tumor or embryonal carcinoma. Report of five cases.

The authors evaluated the effect of adjuvant therapy (preoperative chemotherapy combined with radiotherapy) followed by radical tumor removal in the treatment of children with primary intracranial yolk sac tumor, embryonal carcinoma, or mixed germ cell tumors containing yolk sac tumor components. Between 1988 and 1995, five consecutive patients were treated with adjuvant therapy followed by total tumor removal. The diagnosis was based on markedly elevated concentrations of serum alpha-fetoprotein (AFP) and/or beta-human chorionic gonadotropin (beta-HCG) in four children and the results of biopsy sampling in one child. The chemotherapy regimen consisted of cisplatin (20 mg/m2) and etoposide (60 mg/m2) daily for 5 days (one course) given three times at 4-weeks intervals. Radiotherapy consisted of 30 to 40 Gy to the whole brain or an area including all ventricles and a 15- to 20-Gy boost to the tumor site. Spinal radiation of 25 Gy was added in one patient. In all patients the serum level of AFP and beta-HCG gradually decreased during the adjuvant therapy and disappeared completely on its completion. In two of the five patients the tumor disappeared as well. In the other three patients the tumor size was moderately or markedly reduced and the remaining tumor was totally removed; there were no neurological deficits. Chemotherapy was maintained after the initial treatment and was repeated every 2 to 4 months for less than 2 years. All children are alive and well without recurrence at 33 to 118 months (average 88 months) after the start of adjuvant therapy. Our preliminary results indicate that adjuvant therapy consisting of combination chemotherapy with cisplatin and etoposide and concomitant radiotherapy, followed by removal of the tumor, is highly effective in the treatment of pediatric patients with primary intracranial yolk sac tumor, embryonal carcinoma, or mixed germ cell tumors containing yolk sac tumor components.     

Secondary leukemia following ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors in a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of secondary leukemia occurring in a 31-year-old man who received ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) for a refractory testicular cancer (pathology; Seminoma, Embryonal carcinoma, Yolk sac tumor, Choriocarcinoma) with IIIB2 under Japanese classification, poor-risk group under Indiana classification. The initial levels of serum LDH, AFP and beta-HCG were high at 959 IU/l, 1,452 ng/ml and 800 ng/ml. He received total 11 cycles of systemic chemotherapy (2 cycles of PVB regimen, 4 cycles of PEB regimen, 3 cycles of VIP regimen and 2 cycles of ultra high-dose chemotherapy with PBSCT for pulmonary and para-aortic lymph node metastasis following his initial orchiectomy. The total amount of etoposide (VP-16), cisplatin (CDDP), carboplatin (CBDCA) and ifosfamide (IFM), this patient received was 7,225 mg/m2, 1,510 mg/m2 1,750 mg/m2, and 50.5 g. He has survived with CR of disease. Severe and persistent pancytopenia developed 25 months after his initial orchiectomy. Bone marrow examination showed AML (M2 with eosinophilia) under French-America-British (FAB) classification. Therefore, he was diagnosed as secondary leukemia following high-dose chemotherapy. He received total 6 cycles of systematic chemotherapy for the secondary leukemia in the internal department. He is planing to have bone marrow transplantation. To our knowledge, this is the first reported case in the literature relevant to secondary leukemia following ultra high-dose chemotherapy with PBSCT in testicular tumor in Japan.     

BEP (bleomycin, etoposide, cisplatinum) chemotherapy as an induction therapy of advanced extragonadal germ cell tumor]

Five patients with advanced extragonadal germ cell tumor (EGGCT) were treated with cisplatinum + vinblastine + bleomycin (BVP) or cisplatinum + etoposide + bleomycin (BEP) chemotherapy as an induction therapy. All patients had high levels of tumor markers and multiple distant metastasis in poor nutritious conditions. Two patients given BVP therapy died 6 and 9 months after the chemotherapy. By contrast, three patients given BEP therapy achieved complete remission and were surviving longer than one year without any evidences of disease. Granulocytopenic fever was seen soon after the first course of BEP therapy. Prophylactic granulocyte-colony stimulating factor (G-CSF) treatment, enabled two of them to receive full dose chemotherapy without any fever attacks. In conclusion, BEP chemotherapy is effective to EGGCT as well as far advanced testicular tumors and G-CSF treatment is useful for achievement of induction chemotherapy to advanced germ cell tumors.     

High-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced extragonadal germ cell tumor--a case report]

We reported the experience of high-dose chemotherapy (HDC) combined with peripheral stem cell transplantation (PBSCT) in 29 years-old man with advanced retroperitoneal germ cell tumor accompanied with left supraclavicular lymph node metastases, who obtained complete remission after comprehensive treatment. The initial levels of serum AFP, hCG and beta-hCG were high at 30.2 ng/ml, 14,000 mIU/ml and 66 ng/ml, respectively. After 3 courses of chemotherapy (BEP regimen), while left supraclavicular lymph node swelling was disappeared, the retroperitoneal mass lesion persisted on CT scan. Not all of 3 markers fell to the normal range. After myelosuppressive chemotherapy (etoposide 500 mg/m2 Day 1-3), PBSCs were collected by two consecutive apheresises on Day 17 and 18. In total, 19.5 x 10(6)/kg CD 34 positive cells were obtained. The patient underwent PBSCT (all CD 34 positive cells were infused) on Day 0 following HDC (CBDCA 250 mg/m2/day, etoposide 300 mg/m2/day, IFM 1.5 g/m2/day, Day-7(-)-3, respectively). He became severely leukopenic and thrombopenic with nadir of 200/microliter on Day 6 and 2 x 10(4)/microliter on Day 2, respectively. By administration of platelet transfusion and G-CSF, the white blood cell counts and thrombocyte counts recovered to 6,400/microliter and 4.1 x 10(4)/microliter on Day 10, respectively. Microbiologically enterocolic and respiratory tract infections occurred with elevated body temperature (> 40 degrees C). Antibiotic and antimycotic treatments were continued until disappearance of all clinical and microbiological evidence. He was kept for 10 days in clean room. After HDC, all markers fell to the normal range, but the retroperitoneal residual mass still persisted. Resection of the residual mass and retroperitoneal lymph node dissection were performed with pathological examination revealing tissue necrosis without viable cell. The patient has survived with no sign of the disease for 9 months.     

Sarcomatoid renal cell carcinoma with a chromophobe component producing beta-human chorionic gonadotropin

We report a case of sarcomatoid renal cell carcinoma with a chromophobe component showing significant elevation of beta-human chorionic gonadotropin (beta-HCG) in the peripheral blood. A 35-year-old man was hospitalized because of a large tumor of the left kidney and elevated serum levels of beta-HCG. Extended nephrectomy was performed, after which the serum beta-HCG level decreased. However, 3 months later, masses were discovered in the left renal bed and in the lung in association with elevated serum levels of beta-HCG. The patient was rehospitalized and received combination therapy with interferon-alpha and doxorubicin-based multiple chemotherapy (cyclophosphamide, vincristine, doxorubicin, and dacarbazine). The recurrent mass responded extremely well to treatment, and beta-HCG normalized. However, the patient died 14 months after nephrectomy because of eventual resistance to chemotherapy. Sarcomatoid renal cell carcinoma containing beta-HCG positive cells were pathologically diagnosed with immunohistochemical staining in the left kidney. Sarcomatoid renal cell carcinoma is a variant of renal adenocarcinoma which has a poor prognosis. This patient had an extremely rare sarcomatoid renal cell carcinoma associated with serum levels of beta-HCG which were elevated and strongly correlated with morphologic cancer activity. beta-HCG might be a useful serum marker for detecting and monitoring this renal cell carcinoma.     

Paclitaxel, ifosfamide, and nedaplatin (TIN) salvage chemotherapy for patients with advanced germ cell tumors

BACKGROUND: The paclitaxel, ifosfamide, and cisplatin regimen has been used to treat metastatic testicular cancer with successful results. We investigated the usefulness of a paclitaxel, ifosfamide, and nedaplatin (TIN) regimen as salvage therapy for patients with advanced testicular germ cell tumors (GCTs). METHODS: Eight patients with advanced GCTs were treated with TIN. The treatment was performed as salvage therapy for cases refractory to therapies, such as bleomycin, etoposide and cisplatin, and irinotecan with nedaplatin. The TIN regimen consisted of paclitaxel (200 mg/m(2)) by 24-h infusion on day 1, followed by ifosfamide (1.2 g/m(2)) infusions over 2 h on days 2-6, and nedaplatin (100 mg/m(2)) given over 2 h on day 2. RESULTS: Seven out of eight patients achieved a disease-free status after chemotherapy, followed by surgical resection of the residual tumor. Six of the seven patients have continued to show no evidence of disease after salvage therapy, with a median follow-up period of 27 months, but one patient developed a 'growing teratoma syndrome' in the mediastinum 31 months after TIN chemotherapy. All patients developed grade 4 leukocytopenia. However, it could be managed by using granulocyte colony-stimulating factor. Only one patient developed grade 2 sensory neuropathy and no patient developed nephrotoxicity. CONCLUSION: The TIN regimen was efficacious and well-tolerated as salvage chemotherapy for Japanese patients with advanced GCTs.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

Between June 1998 and August 2000, five patients with germ cell tumor were treated with high-dose CEI: carboplatin (1,250 mg/m2), etoposide (1,500 mg/m2), and ifosfamide (7.5 g/m2), followed by peripheral blood stem cell transplantation (PBSCT) at Yokohama City University Hospital. All patients were classified into either poor risk group of International Germ Cell Consensus Classification or advanced extent of Indiana University stage, and received one cycle of high-dose CEI after 4-6 cycles of standard PEB (cisplatin, bleomycin, vinblastin) therapy. Three of the patients achieved complete response, one achieved partial response and one achieved no change after whole treatment. There were no fatal complications and no treatment-related deaths.     

A case of extragonadal germ cell tumor with inferior vena caval tumor thrombus]

We report a case of retroperitoneal extragonadal germ cell tumor with tumor thrombus in the inferior vena cava. The patient referred to our hospital with lumbago. Computed tomography (CT) showed a bulky mass in the retroperitoneum. The levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-HCG) in the serum were elevated. Histological examinations indicated embryonal cell carcinoma. Bilateral testicles did not contain any palpable mass upon careful palpation. No tumor mass was detected in the bilateral testicles on ultrasonography. Clinically, the diagnosis was a retroperitoneal extragonadal germ cell tumor associated with para-aortic lymph-node involvement. After the combination chemotherapy (BEP 1 course and EP 3 courses), the tumor mass was reduced in size and the tumor marker was normalized. Retroperitoneal lymph node dissection (RPLND) was performed and tumor thrombus in the inferior vena cava was resected. There was no involvement of the viable cells in the resected tumor. The patient has been in good condition with no evidence of disease.     

Salvage chemotherapy with methotrexate,etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: A preliminary report

The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high‐dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of β‐human chorionic gonadotropin (β‐HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1–5, etoposide: 100 mg/body on days 1–5) was subsequently administered. After MEA therapy (median: 3 cycles), serum β‐HCG was normalized in five of the nine patients. Of these five, three achieved long‐term disease‐free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of β‐HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment‐related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.     

High-Dose Chemotherapy plus Stem Cell Transplantation in Advanced Germ Cell Cancer: A Review

Context

High-dose chemotherapy (HDCT) with stem cell transplantation (SCT) has been investigated as a treatment strategy for advanced germ cell cancer (GCC) for >2 decades. In an effort to improve on the overall cure rates of 80% achievable with conventional chemotherapy, researchers have investigated this therapeutic option as a first-line therapy for those with poor-prognosis disease and as a salvage therapy for those with relapsed or refractory disease.

Objective

The primary objective of this review is to define the role of HDCT plus SCT in advanced GCC. Prognostic indicators for this group of patients are also presented.

Evidence acquisition

A Medline search of English-language literature was performed to identify studies published in the last 20 yr relating to the use of HDCT plus SCT in advanced GCC. Phase 1, phase 2, and phase 3 trials were included, as were retrospective reviews and meta-analyses.

Evidence synthesis

Phase 2 trials investigating HDCT plus SCT as a therapeutic option for advanced germ cell cancer have indicated a survival advantage over conventional chemotherapy. This has not been confirmed in the phase 3 setting. Alternative chemotherapeutic strategies and options following failure of HDCT plus SCT are discussed.

Conclusions

Studies to date have not indicated a survival advantage for the use of HDCT plus SCT in advanced germ cell cancer. Many questions, however, remain unanswered, and further research is required to identify whether optimising the strategy of HDCT plus SCT will improve outcome in this predominantly young group of patients.