High dose chemotherapy and autologous bone marrow transplantation for advanced germ cell tumor

Six patients, with advanced germ cell tumor refractory to prior chemotherapy including cis-platinum and etoposide, were treated by high dose chemotherapy and autologous bone marrow transplantation. Etoposide (1200-1800 mg/m2), cyclophosphamide (120 mg/kg) and cis-platinum (60-120 mg/m2) were given and the autologous bone marrow was infused 72 hours after the last dose of chemotherapy. Two patients were treated by high dose chemotherapy three times. The regimen of the third high dose chemotherapy was etoposide (1800 mg/m2), cyclophosphamide (120 mg/kg), adriamycin (80 mg/m2), ACNU (200 mg/m2) and 254S (100 mg/m2). One patient died of cerebral hemorrhage 7 days after ABMT. Of the 5 patients evaluable for response, 4 responded: one patient obtained a complete response and 3 a partial response.     

Rapidly recycled, intensive alternating chemotherapy in heavily pretreated progressive nonseminomatous germ cell tumors a feasibility study

To evaluate the feasibility and the efficacy of an intensive alternating chemotherapy regimen with hematopoietic growth factor support in the late salvage treatment of patients with metastatic nonseminomatous germ cell tumors (NSGCT), 14 patients with refractory or recurrent disease were treated with a combination regimen of vinblastine and bleomycin (VB) followed by three weekly cycles of BOP (bleomycin + vincristine + cisplatin) and subsequent CISCA (cyclophosphamide + doxorubicin + cisplatin) cycles. All patients experienced a grade 3 or 4 neutropenia despite prophylactic growth factor support; II patients required empiric antimicrobial therapy during the chemotherapy program. No toxic death or other significant adverse effect was seen. Eight patients achieved a complete remission and three patients had a partial remission with normalization of serum tumor markers at completion of chemotherapy. Four patients received high-dose chemotherapy with autologous bone marrow transplantation as consolidation therapy and one patient underwent a salvage surgery. Three patients remain free of disease at over 18, 26, and 36 months after therapy. We demonstrate here the feasibility of an intensive alternating chemotherapy schedule in the late salvage treatment of progressive NSGCT. Our results also suggest that the combination of such an approach with high-dose chemotherapy (HDCT) and/or surgery can be used in a curative attempt after the failure of first line salvage therapy.     

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.     

Myelodysplastic syndrome following therapy for brain tumor--two case reports

A 3-month-old boy and a 29-year-old woman presented with myelodysplastic syndrome (MDS) following therapy for primary malignant brain tumor. Both received intensive alkylating agent doses for induction and maintenance chemotherapy combined with craniospinal or cranial radiation for medulloblastoma and anaplastic astrocytoma, respectively. They developed refractory anemia and pancytopenia. Approximately 9 years after the completion of induction chemoradiotherapy, chromosomal analysis of bone marrow cells resulted in the diagnosis of MDS. The boy died of leukemic evolution 15 months later, the woman died of hematopoietic failure 3 months later. The most common symptom of MDS is refractory anemia, either alone or as part of bi- or pancytopenia. Clonal proliferation with chromosomal analysis of bone marrow cells establishes the diagnosis of MDS. Patients with malignant brain tumors are at risk of the development of MDS as a late complication of chemotherapy based on high cumulative doses of alkylating agents.     

Salvage chemotherapy with paclitaxel, ifosphamide and nedaplatin for relapsed or refractory germ cell cancer

PURPOSE: Only 20-30% of patients with cisplatin refractory or relapsed germ cell cancer will remain continuously disease free with salvage chemotherapy. Paclitaxel is a potent anticancer agent against a variety of solid cancers. The present study investigated the chemotherapy with paclitaxel in combination with nedaplatin, which is a derivative of cisplatin, and ifosphamide as salvage chemotherapy for cisplatin refractory germ cell cancer. MATERIAL AND METHODS: The combination chemotherapy consisted of paclitaxel 210 mg/m2 on day 1, nedaplatin 100 mg/m2 on day 2 and ifosphamide 1.2 g/m2 on day 2-day 6 every three weeks. Fourteen patients with cisplatin refractory germ cell cancer, ranging in age from 17 to 44 years were enrolled onto the study. RESULTS: Fourteen patients were evaluated for response and toxicity. Patients received 1-14 cycles of the combination chemotherapy. The median duration of follow-up was 34 months (10-64 months). Response rate was 57.1% (CR / PR(m-):8 cases, NC:5 cases, PD:1 cases). Seven patients remain alive without disease. However, 5 patients died of the disease. All patients had grade 3 or 4 hematological toxicity. CONCLUSION: This study demonstrates that the chemotherapy with paclitaxel in combination with nedaplatin and ifosphamide showed a significant anticancer activity for patients with cisplatin refractory or relapsed germ cell cancer. These findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for cisplatin refractory or relapsed germ cell cancer.     

Treatment for Advanced Testicular Cancer with High-Dose Chemotherapy and Autologous Blood Stem Cell Transplantation

Background This study was carried out to investigate the efficacy and safety of high-dose chemotherapy (HDC) for the treatment of patients with advanced testicular cancer.
Methods Seven patients were treated with high-dose carboplatin, etoposide, and ifosfamide followed by autologous blood stem cell transplantation. One patient received 1 cycle, 4 patients received 2 cycles, and 2 patients received 3 cycles of HDC. We performed a total of 15 autologous blood stem cell transplantations: 8 with autologous bone marrow; 6 with peripheral blood stem cells; and 1 with peripheral blood stem cells in addition to autologous bone marrow.
Results Four of the 7 patients achieved a pathologic complete response via early use of HDC and additional salvage surgery. All 4 patients are still alive without evidence of disease at 12, 30, 33, and 54 months, respectively. One patient is alive with active disease at 35 months. Two patients refractory to conventional chemotherapy died of progressive disease at 5 and 27 months, respectively. The hematologic recovery after HDC was rapid, and peripheral blood stem cells tended to have shorter hematologic recovery compared with those from autologous bone marrow, although the difference was not significant. Nonhematologic toxicity was usually mild and manageable.
Conclusion High-dose chemotherapy, followed by autologous blood stem cell transplantation, may be safe and effective for patients with advanced testicular cancer, particularly when early use of HDC is conducted for chemotherapy-sensitive patients. A further large, long-term, follow-up study will be needed to define the role of HDC.     

Refractory germ cell cancer of testis treated by salvage high-dose chemotherapy: report of three cases

We reported three cases (42, 20 and 18-year-old men) of advanced nonseminomatous testicular germ cell cancer treated by salvage high-dose chemotherapy (HDC) supported by peripheral blood stem cell autotransplantation. Two cases which had been refractory to (B) EP (bleomycin, etoposide, cisplatin) and VIP (etoposide, ifosfmide, cisplatin) chemotherapies received one course of high-dose CEI (carboplatin 1,250 mg/m2, etoposide 1,500 mg/m2 and ifosfamide 7.5 g/m2), and the other case had been refractory to PVB (cisplatin, vinblastine, bleomycin) and VIP chemotherapies received one course of high-dose CEI and high-dose CCT (carboplatin 800 mg/m2, cyclophosphamide 6 g/m2 and thiotepa 720 mg/m2). Only one case achieved an incomplete remission by HDC, which was verified as a pathological complete response at the following salvage surgery, and has been alive with no evidence of disease for 68 months. The others achieved no change of disease following HDC and died from cancer progression. Hepatotoxicity, neurotoxicity and severe depression occurred, but not fatal in 2 cases.     

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.     

Occult lumbar vertebral body metastasis of non-seminomatous germ cell tumor eradicated by radiation and salvage surgery 9 years after initial onset

In this report we describe a case of late relapse non-seminomatous germ cell tumor eradicated after 9 years of initial onset. A 20-year-old man complaining of recent aches, vomiting and headaches was diagnosed with right testicular tumor with solitary brain and bilateral lung metastases. At presentation, human chorionic gonadotropin (HCG) was elevated to 22,000 mIU/ml, and alpha-fetoprotein to 79 ng/ml. A right high orchiectomy was performed, followed by a right occipital osteoplastic craniotomy due to the presence of left hemiplesia and anisocoria prior to chemotherapy. Pathologically, the tumors were embryonal carcinoma and yolk sac tumor. The patient received 5 cycles of cisplatin-based PEP chemotherapy (cisplatin, etoposide and peplomycin) after which all the tumor markers fell to within the normal range. The remaining right lung tumor was removed surgically and the remnant lesion was found to be scar tissue. Four years after initial therapy, elevated serum HCG levels were detected. The tumor metastasis showed only HCG elevation responsive to chemotherapy each time followed by relapse and undetectable with all kinds of imaging examinations for 5 years. Finally when the tumor became chemorefractory, conventional computed tomography scan on bone window detected the occult tumor in L4 corporal body. After radiation therapy the tumor was removed by total spondylectomy and there was no viable tumor cells in the specimen pathologically. HCG fell to within normal range according to its half life period after the operation and there is no relapse of HCG after 18 months follow up. CT bone window photography may be sometimes useful to detect occult bone metastasis and salvage surgery combined with radiation therapy may be worth trying in patients with chemorefractory non-seminomatous germ cell tumors.     

New perspectives on therapy for vaginal endodermal sinus tumors

PURPOSE: Malignant germ cell tumors account for 3% of childhood cancers. Endodermal sinus tumor, the most common malignant germ cell tumor, requires treatment primarily with chemotherapy and surgery is reserved as a last resort. It is rare for the vagina to be the primary site of endodermal sinus tumor, and we report on our experiences with this phenomenon at a single institution. MATERIALS AND METHODS: We retrospectively reviewed the clinical features, treatment and outcomes of 3 children with vaginal endodermal sinus tumor. RESULTS: Initial treatment was combination chemotherapy, in 2 patients. alpha-fetoprotein decreased rapidly and returned to normal in both. One patient is disease-free 7 years after chemotherapy and the other patient is currently disease-free with a normal alpha-fetoprotein 3 months after induction chemotherapy. In the remaining case progressive disease developed following initial chemotherapy and subsequent salvage surgery combined with radiation, chemotherapy and ultimately autologous bone marrow transplant was performed. The patient has remained disease-free for 6.5 years since completing this extensive therapy. CONCLUSIONS: Endodermal sinus tumor of the vagina is rare. All of our patients presented with painless bleeding of no obvious source. In such cases one must maintain a high index of suspicion for possible underlying pathological conditions even if ultrasound is negative. Evaluation must include endoscopic examination of the lower genitourinary tract. Bone marrow transplant should be considered as a last therapeutic resort in salvage cases of unresponsive vaginal endodermal sinus tumor.     

Paclitaxel-based chemotherapy for patients with refractory or relapsed nonseminomatous germ cell tumors

Germ cell tumors have been the paradigm for successful solid tumor therapy. With multimodality treatment including surgery and/or chemotherapy and/or radiation therapy 75% of all patients with germ cell tumors will be cured of their malignancy. However, in patients who have primary refractory or relapsed disease, the cure rate is less than 20%. Treatment strategies in this patient population have included: (1) dose intense therapies such as alternating sequential chemotherapy with multiple active regimens given in short intervals, (2) dose dense therapy with high-dose chemotherapy and stem cell support, (3) new agents, and (4) salvage surgery. Prognostic stratification of patients in a salvage setting can help to determine which therapeutic modalities may provide the greatest opportunity for success. The evaluation of new agents has historically occurred in the salvage setting followed by the development of combinations and then advancement to nonsalvage therapy. The introduction of paclitaxel, with its novel mechanism of action and preclinical activity, resulted in its evaluation as a single agent in patients with refractory or relapsed nonseminomatous germ cell tumors. As a single agent, paclitaxel has an overall response rate of 13.3% in a heavily pretreated salvage population. The preclinical evaluation of the combination of paclitaxel and cisplatin allowed for the most appropriate sequencing and dosing of the two agents. In addition, preclinical evaluation suggests that these agents are synergistic as well as active in cisplatin-refractory disease. The combination of paclitaxel and cisplatin was evaluated clinically and demonstrated an overall response rate of 30%. Doxorubicin is an active agent in germ cell tumors and has nonoverlapping toxicity with pactitaxel and cisplatin. The majority of patients treated in a community setting have not had prior exposure to this agent. Therefore, the regime of doxorubicin, paclitaxel, and cisplatin (ATP) was developed and in a small number of patients was utilized in the salvage setting with a 25% response rate. A pilot study with ATP therapy for patients with nonseminomatous germ cell tumors who have disease progression during induction therapy or first and second salvage regimens and who have received a total of more than six courses of prior chemotherapy is ongoing.     

A Case of Myelodysplastic Syndrome in a Liver Transplant Patient

Although the incidence of (myelodysplastic syndrome (MDS)) is higher among heart and lung transplant recipients than the general population, the same has not been shown in liver transplant (OLT) patients. We present the second known case of MDS after OLT. Case reports of MDS in OLT were identified using PubMed. Patient data were gathered from the patient and the medical record.A 54-year-old Caucasian man underwent OLT in 2003 and again in 2004 for hepatitis C-related cirrhosis. In 2007, the patient developed weakness, malaise, and shortness of breath. Laboratory studies revealed pancytopenia. Bone marrow biopsy showed MDS, with refractory anemia and excess blasts-1. The patient underwent chemotherapy and reduction in immunosuppression without a clinical response.Our experience suggested that MDS, although rare, should be considered in the differential diagnosis of pancytopenia after OLT. Once diagnosed, immunosuppression reduction, chemotherapy, and even stem cell transplantation may be the appropriate treatment in selected candidates.     

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.     

Late relapse of metastatic testicular nonseminomatous germ cell cancer: surgery is needed for cure

OBJECTIVE: To identify patients with late relapse of metastatic, nonseminomatous germ cell tumour (NSGCT) and to evaluate the patterns of relapse, treatment and outcome, as such relapse at >2 years after complete remission to treatment for metastatic disease (late relapse) is uncommon, but with prolonged follow-up is becoming increasingly recognized. PATIENTS AND METHODS: Between 1980 and 2004, 1405 patients with testicular GCTs were identified who presented to Southampton University Hospital; 742 had NSGCTs or combined testicular GCTs, of whom 405 received primary chemotherapy for metastatic disease. In all, 329 (81%) patients achieved a complete response (CR) to initial treatment, with 101 of them (31%) requiring surgical resection of residual masses after chemotherapy. Any patient relapsing at >2 years after a CR to initial treatment (late relapse) was assessed in detail. RESULTS: In all, 20 patients had a late relapse, 17 of whom received initial treatment locally and three of whom were initially treated elsewhere. Most (65%) late relapses were asymptomatic and detected by routine cross-sectional imaging or rising levels of tumour markers. Late relapse occurred at a median (range) of 108 (26-217) months (approximately 9 years) after CR. Fifteen (75%) patients underwent only surgery for late relapse, including five who had invasive malignant germ cell cancer within the resected specimens. Fourteen of 15 surgically treated patients remained alive at a median of 44 (9-184) months from initial treatment for late relapse; one had died with progressive recurrent germ cell/epithelial malignancy. Five (25%) patients were initially treated with chemotherapy for late relapse; three of them died from progressive germ cell cancer and the two survivors both had surgical excision of residual abnormalities after salvage chemotherapy. Overall, 15 of 20 (75%) men remain alive with no evidence of disease; one further patient is currently undergoing salvage treatment for his third relapse. CONCLUSION: Late relapse is uncommon after modern therapy for metastatic GCTs. Surgical treatment for localized disease, where possible, is associated with prolonged disease-free and overall survival. By contrast, chemotherapy is associated with a low response rate and a poor outcome.     

Postchemotherapy retroperitoneal lymph node dissection in patients presenting with very high HCG levels

PurposeChoriocarcinoma germ cell tumors are rare and usually present with significantly elevated human chorionic gonadotropin (hCG) levels. When curable, it is felt to be largely a result of chemotherapy. We sought to determine the histologic characteristics for those undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and compare them with metastatic nonseminomatous germ cell tumor (NSGCT) patients with similarly elevated hCG levels.MethodsWe reviewed medical records of men undergoing PC-RPLND between 1988 and 2017 with postorchiectomy, preinduction chemotherapy hCG levels greater than 50,000 mIU/ml. They were stratified by primary tumor histology: Pure choriocarcinoma and mixed NSGCT. Clinical, pathologic, and serologic data were reported and logistic regression was used to assess for predictors of necrosis in the PC-RPLND specimen.ResultsOur cohort consisted of 108 men. The mixed group (n = 91) had a median hCG of 165,177 mIU/ml, a postchemotherapy node size of 4.7 cm, of whom 19.8% also received salvage chemotherapy prior to RPLND. The pure choriocarcinoma group (n = 17) had a median hCG of 170,267 mIU/ml, a node size of 5.1 cm, of whom 17.6% received salvage chemotherapy. 88.2% of patients with choriocarcinoma had necrosis in the PC-RPLND specimen compared with 29.7% of the mixed NSGCT group (P = <0.0001). Controlling for salvage chemotherapy use, prechemotherapy hCG, node size and marker status, choriocarcinoma patients were 20 fold more likely to have necrosis on RPLND specimen (Odds ratio 20.68 [95% confidence interval 5.279–81.114]).ConclusionWhile PC-RPLND is appropriate in patients with residual masses after chemotherapy, patients with pure choriocarcinoma presenting with significantly elevated hCG levels represent a unique patient population where necrosis is found more often than anticipated.     

High-dose chemotherapy with autologous bone marrow transplantation for malignant brain tumors

Three patients with malignant gliomas were treated with the high-dose chemotherapy with autologous bone marrow transplantation. In the first two cases, the autologous bone marrow cells were stored and transplanted 48 hours after single high-dose of ACNU therapy. (800 mg/m2, 600 mg/m2) One died of intratumorous bleeding on the 18th day and the other of pulmonary fibrosis on the 35th day. Their autopsy specimens revealed that most of the tumor had degenerated with only a small portion of viable cells. The third patient was treated with high-doses of ADM (100 mg/m2), VCR (1.5 mg/m2), DDP (80 mg/m2), and EX (800 mg/m2) within eight days, prior to the cryopreserved bone marrow transplantation. Granulocytes and platelets began to increase from ten days after the transplantation and became normalized within three weeks thereafter. CT scan performed six months after the chemotherapy revealed 89% reduction of the tumor. The number of our cases is still small, but the results showed that the autologous bone marrow transplantation made high-dose chemotherapy possible. The necessity for cryopreservation of bone marrow was discussed.     

VM-26 and VP-16 salvage therapy for refractory germinal testicular cancers

Thirteen evaluable patients with germinal testicular cancers failing to be cured with first-line therapy (refractory) were treated by salvage chemotherapy. Ten patients received salvage chemotherapy with VM-26 (50 mg/m2, twice a week X 6 weeks) and cisplatin (CDDP, 20 mg/m2 for 5 consecutive days every 3 weeks for 3-4 times) (P-VM), 3 patients were also treated by radiation therapy, and 3 patients received VP-16 (100 mg/m2) and CDDP (20 mg/m2) (P-VP), all given daily for 5 consecutive days every 3-4 weeks for 4-5 courses. Of 13 evaluable patients, 6 (46%) had complete response (CR) (three cases were also treated with radiation therapy), 4 (31%) achieved partial response (PR), and 3 (23%) had no response. Limited to 7 patients treated with only P-VM therapy, there were 3 (43%) CR and 4 (57%) PR. Nine patients (69%) remained alive and were continuously disease free 18 to 84 months (median 48 months). Hematologic toxicity was severe, but with no death related to sepsis. Salvage chemotherapy with VM-26 or VP-16 and cisplatin offers potentially curative treatment to patients with refractory testicular cancer. The addition of radiation therapy to salvage chemotherapy was also effective.     

Chemotherapy-resistant germ cell cancer of the testis treated by salvage surgery: a case report

A 38-year-old patient who had a non-seminomatous testicular cancer was treated by resection of the retroperitoneal metastatic mass that had proven refractory to bleomycin, etoposide and cisplatin (BEP) and paclitaxel, ifosfamide and cisplatin (TIP) chemotherapies. Although salvage chemotherapy was given against the chemorefractory metastatic lesions in the retroperitoneum, the serum alpha-fetoprotein level elevated to 3,252 ng/ml. Retroperitoneal lymph node dissection was performed, and viable cells were identified histopathologically in the resected tissues. The serum AFP level normalized after surgery. No recurrence has been observed for 22 months postoperatively. This experience indicates that salvage surgery even under high serum marker levels may have a beneficial outcome for selected cases of chemotherapy-resistant germ cell tumors.     

Salvage chemotherapy for patients with germ cell cancer

Bleomycin, etoposide and platinum (BEP) therapy is used on patients with metastatic germ cell cancer but approximately 20-30% of these patients fail to achieve a durable complete response following the administration of BEP therapy. For such patients, salvage chemotherapy is subsequently considered. Although either VIP of VeIP therapy had been tended to be selected as salvage chemotherapy, recent studies have suggested two novel strategies as an alternative to conventional regimen for salvage chemotherapy. One is high-dose chemotherapy, while the other is the use of a regimen containing newly developed chemotherapeutic agents. In this study, we summarize the current status of therapeutic strategy for patients with metastatic germ cell cancer refractory to BEP therapy, and then present the experience with salvage chemotherapy at our institution.     

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.