Chemotherapy For Germ Cell Tumors Research Articles

Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

IntroductionDevelopment of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically.Case presentationWe report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation.ConclusionThe presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma). In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

A case of growing teratoma syndrome in mixed germ cell tumors of the ovary

Growing teratoma syndrome (GTS) is an increase in tumor size containing only mature teratoma component, during or after chemotherapy for germ cell tumors. A surgical resection is important to confirm diagnosis and is considered as the most appropriate therapeutic management. GTS is rare event in association with ovarian germ cell tumors. In this report, we present a case of GTS which occurred following the treatment of mixed ovarian germ cell tumor with immature teratoma and endodermal sinus tumor. The patient was given adjuvant chemotherapy consisting of six cycles of etoposide and cisplatin. Abdomen pelvis computed tomography performed after chemotherapy demonstrated no evidence of recurrence. She is on regular follow up and remained disease-free for 8 months following second surgery.

Phase II trial of aprepitant on days 1 to 7 for patients with germ cell tumors having cisplatin on days 1 to 5.

e19577 Background: There is no established aprepitant-containing anti-emetic regimen for multi-day, cisplatin-based chemotherapy. The aim of this single-arm, multi-centre, phase II trial was to determine the efficacy of giving aprepitant for 7 days to patients having 5 days of cisplatin and etoposide as first line chemotherapy for germ cell tumors (BEP, accelerated BEP, or EP). Methods: Patients received oral aprepitant 125 mg day 1 and 80 mg days 2 to 7, a 5HT3 antagonist days 1 to 5, and dexamethasone 8 mg days 1 to 8. The primary endpoint was “nil emesis” during days 1 to 7 of cycle 1 assessed by patients with a self-completed diary. Key secondary endpoints are listed in the table. Results: 50 patients recruited from May 2009 to December 2010 had a median age of 30 years and ECOG performance status 0 or 1. Compliance rates for anti-emetics during cycle 1 were 92% for aprepitant, 86% for dexamethasone, and 96% for 5HT3 antagonist. There were no serious unexpected adverse events attributed to aprepitant. Efficacy results are tabulated. Conclusions: The nil emesis rate during days 1 to 7 of 84% (95% CI 70%, 93%) was substantially better than the historical control rate of 50%. These results support the safety, efficacy and further consideration of using aprepitant on days 1 to 7 for patients with germ cell tumours having cisplatin on days 1 to 5. Supported in part by supply of drug from Investigator-Initiated Studies Program of Merck and Co. and research grant from Merck Sharp & Dohme (Australia) Pty Limited. Cycle 1 Historical control of 5HT3 antagonist and dexamethasone (Einhorn, Supp Care Cancer 2007; 15: 1293) Day 1 Days 1 to 5 Days 1 to 7 Day 1 Days 1 to 5 Nil emesis 98% 88% 84% 88% 51% Nil emesis and nil rescue therapy 84% 47% 43% 83% 34% No significant nausea (< 2/10 on VAS) 84% 45% 41% *Currently awaiting diary for one patient.

Growing teratoma syndrome of the Ovary: A case report with FDG ‐PET findings

Growing teratoma syndrome (GTS) is defined as enlarging masses during or after chemotherapy for germ cell tumors, and containing only mature teratoma components. A surgical resection is important to confirm a diagnosis and thereby result in the resection of the most appropriate therapeutic management. GTS is a rare event in association with ovarian germ cell tumors. This report presents a case of a 36-year-old female treated surgically for GTS found during the follow-up after chemotherapy and the primary surgical resection of a malignant immature teratoma. Those masses showed fluorodeoxyglucose positron emission tomography positivity and elevated serum CA19-9 prior to the second operation. The histology revealed a mature teratoma. The patient has been disease free for 6 months after the second operation.

Long-Term Cardiovascular Risk Following Platinum-Based Chemotherapy for Germ Cell Tumors

Background Germ cell tumors (GCTs) are one of the most curable of the solid neoplasms. They are highly sensitive to platinum-based chemotherapy, which contributes to 5 - year survival rates exceeding 90%. Any late effects of treatment are a key consideration when treating a highly curable disease in a young population. There is good evidence that platinum-based chemotherapy increases the risk of cardiovascular morbidity and mortality late in life; the exact nature of the risk is not well understood, nor is there any consensus on a mechanism for this effect. This article examines the current literature to assess the nature and size of the risk posed, and considers possible mechanisms for the effect. We consider the implications of treatment for GCT with platinum-based chemotherapy, as well as the implications for long-term follow-up and optimal clinical care of patients requiring systemic therapy. Discussion

Outcome analysis of patients with transformed teratoma to primitive neuroectodermal tumor

BackgroundThe emergence of a primitive neuroectodermal tumor (PNET) within a germ-cell tumor (GCT) is rare. We assess the prognosis and response to treatment. Patients and methodsEighty-one patients were identified. Selected patients were treated with cyclophosphamide 1200 mg/m2, doxorubicin 75 mg/m2, and vincristine 2 mg i.v. alternating with ifosfamide 1.8 g/m2 × 5 days plus etoposide 100 mg/m2 × 5 days (CAV/IE). Ewing's sarcoma (EWS) translocation was assessed using a FISH-based method. ResultsMedian follow-up was 41 months. Seventy-six patients had PNET in the primary tumor or in initial metastasis. Five harbored PNET only at relapse. Twenty-six of 76 underwent primary retroperitoneal lymph node dissection, 13 of whom had retroperitoneal PNET and four are dead of disease (DOD). Fifty of 76 were initially treated with GCT chemotherapy (n = 49) or CAV/IE (n = 1). Twenty-seven of these 50 underwent complete postchemotherapy resection of residual PNET and 17 are DOD. Ten patients received CAV/IE. Eight achieved an objective response, and five are currently alive. One of the 14 specimens examined carried the EWS translocation. ConclusionsPNET of GCT origin is associated with an adverse outcome. For low-volume disease, surgery is the optimal initial therapy. CAV/IE may have a role in patients with unresectable disease.

Pulmonary Metastasectomy: A Moving Target

For at least 60 years, surgical resection has been a widely used approach to the management of patients with lung metastases from a variety of solid tumors. For many of these patients, surgical resection has provided the only potentially curative treatment. Analyses of numerous retrospective series have led to well-accepted surgical selection criteria: a primary tumor that has been definitively controlled, metastases limited to the lung that can be completely resected, ability of the patient to tolerate the planned operation, and lack of a better alternative treatment. The number of lung metastases, the disease-free interval since treatment of the primary tumor, the tumor doubling time, the presence of lymph node metastases, the histology of the primary tumor, and in some instances, elevated serum markers such as carcinoembryonic antigen are known to influence outcome and may be incorporated into the decision of whether to offer surgery to the patient. However, there remain many controversial aspects to

Retroperitoneal lymph node dissection after chemotherapy for germ cell tumours: is a full bilateral template always necessary?

To evaluate the long-term oncological outcome in selected patients treated for nonseminomatous germ cell tumours (NSGCT) with a retroperitoneal lymph node dissection after chemotherapy (pcRPLND) and not using the full bilateral template. From 1988 to 2005, 102 patients with retroperitoneal stage II NSGCT, who at initial presentation had metastases in the primary retroperitoneal site only, had pcRPLND within a restricted template, whether computed tomography showed complete or incomplete remission. In all, 78 patients had a unilateral template dissection and 24 an open modified template dissection. Of the 102 patients, 30 had stage IIC, 63 IIB, and nine tumour marker-positive stage IIA disease. Active tumour was found in two RPLND specimens; mature teratoma in 46 of the 102 patients, and necrosis/fibrosis in 54. Antegrade ejaculation was preserved in all 78 patients who had unilateral RPLND and in 18 of 24 who had a modified RPLND (overall antegrade ejaculation rate 94%). During a median follow-up of 102 months there were only three recurrences, two outside the retroperitoneum and one in the retroperitoneum. Only the latter was retrocaval, above the level of the inferior mesenteric artery within the boundaries of a full bilateral RPLND. This patient had had left unilateral template dissection after chemotherapy for IIC disease which was restricted to the para-aortic nodes. In a selected group of patients with stage II NSGCT, pcRPLND within the modified template might be oncologically efficient and allow ejaculation to be preserved.

Cardiovascular events in survivors of high‐dose chemotherapy for germ cell tumors

The objective was to investigate cardiovascular complications in long-term survivors treated by high-dose chemotherapy. We analyzed 13 previously successfully treated metastatic germ cell cancer patients. The patients ranged in age from 16 to 38 years (median: 27 years). Patients were treated by high-dose ifosfamide, carboplatin and etoposide (ICE) or high-dose etoposide, ifosfamide and cisplatin (VIP). In a minimal follow-up of 48 months, the incidence of cardiovascular events and the accumulated doses of platinum were analyzed from the total amounts of cisplatin and/or carboplatin. The calculated accumulated doses of platinum ranged from 487 to 4302 mg (median: 2297 mg). Cardiovascular events were observed in two patients who received cumulative doses of more than 3000 mg of platinum. Survivors of high-dose chemotherapy may have a risk of developing cardiovascular complications during the early phase of follow-up. In particular, patients who have received carboplatin-based high dose chemotherapy require careful observation.

Growing teratoma syndrome of ovary

Growing teratoma syndrome is an increase of tumor size containing only a mature teratoma component, during or after chemotherapy for germ cell tumors. Mature teratomatous elements are chemoresistant and have to be resected surgically. We describe three patients with malignant immature teratoma treated with chemotherapy and surgical resection. All three had an increase in the size of the mass after chemotherapy, surgery was possible, and histology revealed mature teratoma. One of the patients showed fluorodeoxy glucose positron emission tomography (FDG-PET) positivity for growing teratoma syndrome, but the histology revealed only mature teratoma. All three patients are alive, at 55, 72, and 103 months' follow up after the initial diagnosis. Data collected from the literature are reviewed. Early recognition of this syndrome is essential as it offers hope for curative resection and avoids the use of ineffective chemotherapy.

Outcome in 41 patients with late relapse germ cell tumors (GCT) treated with high-dose chemotherapy (HDCT)

5086 Background: The management of patients (pts) with late-relapse GCT and unresectable tumors or very high tumor markers is controversial. Methods: A total of 41 late-relapse pts were identified among a group of 216 pts with refractory or relapsed GCT who were treated in an open, prospective, randomized, multicenter phase III trial. Late relapse was defined as any relapse occurring more than 2 years after completion of initial chemotherapy for GCT. Treatment consisted of either one cycle cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE, arm A) or of three cycles of VIP plus one cycle high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2 and cyclophosphamide 6,400 mg/m2 (CEC, arm B). Each HDCT was followed by reinfusion of autologous peripheral blood progenitor cells. Results: Overall 20 pts with late-relapse GCT received sequential HDCT and 21 pts single HDCT when the study was stopped due to excess treatment-related mortality in arm B; median time to late relapse in 41 pts was 5.4 years (range 2–18 years); 8/41 (20%) pts had seminomatous GCT, 32/41 (78%) pts had nonseminomatous GCT with or without teratoma; one pt (2%) had unknown GCT histology. No non-GCT histologies were included. The retroperitonum was most commonly involved in 30/41 (73%) pts. 29 of 41 (71%) pts had unresectable, multifocal disease and 20/41 (49%) pts also had very high markers. A complete remission to chemotherapy alone was achieved in 4/41 (10%) pts, 16/41 (39%) pts achieved a partial remission with negative tumor markers. The remaining 21/41 (51%) either had a transient or no response despite HDCT. Residual tumor resections were performed in 17/41 (41%) pts. Residual tumor histology was viable cancer in 8/17 (47%) pts, teratoma in 4/17 (24%) pts and necrosis in 5/17 (25%) pts. With a minimum follow-up of 1 year and a median follow-up of 3 years the estimated Kaplan-Meier rates are 17%, 20% and 32% for event-free, progression-free and overall survival. Conclusion: Treatment outcome after HDCT was inferior in late-relapse pts compared to the group of pts who relapsed within less than 2 years. Despite an overall poor prognosis, HDCT can still result in long-term remissions in selected late-relapse GCT pts. No significant financial relationships to disclose.

Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer

The aims of this study were to assess the safety and antiemetic efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ cell tumors. Forty-one men undergoing 5-day cisplatin-based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days. Efficacy endpoints included emesis, intensity of nausea and its interference with patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was studied for electrocardiograph effects and pharmacokinetic evaluation. This multiple-day antiemetic regimen was safe, with headache and constipation the most common treatment-related adverse events, mostly mild. Neither adverse events nor electrocardiographic changes appeared to increase in frequency, duration, or intensity over time despite a 1.42-fold systemic accumulation of palonosetron with repeated doses. The majority of patients had no emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate-to-severe nausea, and did not require rescue medication. Most patients reported that nausea had no significant effect on daily functioning on days 1-4 (72%) and days 5-9 (85%). Palonosetron on days 1, 3, and 5, along with a regimen of dexamethasone, was safe and well tolerated and effectively controlled both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy for testicular cancer.

Phase II Study of Paclitaxel Plus Gemcitabine Salvage Chemotherapy for Germ Cell Tumors After Progression Following High-Dose Chemotherapy With Tandem Transplant

To determine long-term survival and potential cure with salvage chemotherapy with paclitaxel plus gemcitabine after progression after both cisplatin combination chemotherapy and subsequent high-dose chemotherapy with tandem transplantation. One hundred eighty-four patients received salvage high-dose chemotherapy at Indiana University (Indianapolis, IN) from February 1996 to December 2004. After further evidence of progressive disease, 32 patients were subsequently treated with paclitaxel 100 mg/n2 over 1 hour plus gemcitabine 1,000 mg/m2 over 30 minutes, days 1, 8, and 15 every 4 weeks for a maximum of six courses. This is a retrospective review of this patient population. Patients were evaluated for response, duration of response, and survival. Patients were ineligible if they received prior paclitaxel or gemcitabine. Ten (31%) of 32 patients achieved objective response, including four partial remissions (2- to 6-month duration) and six complete responses (CRs). Four of these six CRs (12.5% of total patient population) are continuously disease free (NED) with paclitaxel plus gemcitabine alone (no postchemotherapy surgery) at more than 20, 40, 44, and 57 months from start of paclitaxel plus gemcitabine, respectively. One additional CR is currently NED more than 63 months after paclitaxel plus gemcitabine with two subsequent resections of carcinoma. Long-term disease-free survival is possible with paclitaxel plus gemcitabine in this patient population that progressed after high-dose chemotherapy, and had not received prior paclitaxel or gemcitabine.

A postulated role of testosterone for prevention of cisplatin gonadal toxicity

Testicular cancer is the most common solid tumor in young men. It has become one of the most curable solid neoplasms by applying multidisciplinary treatment approaches and new chemotherapeutic drugs. Cisplatin based chemotherapy as the most efficient chemotherapy of germ cell tumors has severe deleterious effects on all stages of spermatogenesis by various direct and indirect mechanisms. By marked improvement in oncologic control, prognosis and survival of patients with testicular cancer, their fertility, as one of the essential aspects of quality of life, is a matter of great concern. Since the probability and severity of spermatogenesis impairment is quite unpredictable during a course of cisplatin based chemotherapy, protecting the spermatogenesis during that phase by administration of exogenous testosterone in order to reduce the proliferation rate of germ cells would seem to be beneficial.

Heart Failure Resulting from Chemotherapy for Testicular Neoplasm: A Follow-Up on a Patient Reported 20 Years Earlier

Heart Failure Resulting from Chemotherapy for Testicular Neoplasm: A Follow-Up on a Patient Reported 20 Years Earlier

A decision analysis on the balance between cancer survival and cisplatin ototoxicity in children with germ cell tumors

8502 Background: Parents and childhood cancer survivors were asked to judge whether an increased survival rate in high-dose cisplatin chemotherapy for germ cell tumors was worth the increased risk ...

Extensive Deep Venous Thrombosis Associated with Chemotherapy for Testicular Cancer: A Case Report with Review of the Literature

The authors report a case of an extensive deep venous thrombosis occurring as a complication of chemotherapy with cisplatin, bleomycin and etoposide for a testicular germ cell tumour. During the first cycle of chemotherapy, the patient developed a dramatic picture of deep venous thrombosis, extending from the popliteal and iliofemoral veins up to the thoracic vena cava, close to the right atrium. Progression of thrombosis to the renal veins resulted in acute renal failure requiring dialysis. There are no reports in the literature of such an extensive thrombosis associated with this regimen. Of note, the remarkable results obtained with the early institution of thrombolytic therapy with streptokinase. Thromboembolic events are potentially lifethreatening complications that seem to occur more frequently than expected in patients receiving chemotherapy for germ cell tumours, in spite of young age. Preventive measures should not be overlooked in this setting. LIST OF ABBREVIATIONS GCT= germ cell tumours CMF= cyclophosphamide, 5-fluorouracil, methotrexate CMF/tam= cyclophosphamide, 5-fluorouracil, methotrexate, tamoxifen DVT= deep venous thrombosis BEP = bleomycin, etoposide, cisplatin TT= thrombolytic therapy DHL= lactate dehydrogenase β-hCG= human chorioninc gonadotropin β-subunit AFP= alphafetoprotein IV= intravenously RP= Raynaud phenomenon SH= systemic hypertension PVB= cisplatin, vinblastin, bleomycin FSH= follicle stimulating hormone LH= luteinizig hormone PTE= pulmonary thromboembolism

Long-Term Complications of Chemotherapy for Germ Cell Tumours

Long-Term Complications of Chemotherapy for Germ Cell Tumours

Secondary leukemias in refractory germ cell tumor patients undergoing autologous stem-cell transplantation using high-dose etoposide.

To quantify the risk of secondary leukemias in relapsed testicular cancer patients undergoing autologous stem-cell transplantation with high-dose etoposide. Single institution, retrospective study of germ cell tumor patients who underwent autologous transplantation using high-dose etoposide from 1987 to 2001. One hundred thirteen patients received high-dose etoposide and carboplatin followed by autologous stem-cell transplantations for germ cell tumors. Follow-up ranged from 12 to 166 months (median, 51 months). Three patients (2.6%; 95% CI, 0.55% to 7.50%) subsequently developed leukemia at an average of 16 months post-autologous transplantation (range, 11 to 21 months). All three had received tandem transplantations and had been heavily pretreated, including at least one prior cycle of etoposide. Following autologous transplantation, all three patients exhibited refractory cytopenias before developing overt leukemia. All leukemias were of myeloid lineage. One patient developed an M2 with a t(8,21) chromosomal translocation; another, an M5 with a t(11,19); and one patient exhibited an unclassified leukemia with cytogenetic abnormalities resulting in monosomy for 7p and partial monosomy of 7q. Treatment of the leukemias involved allogeneic bone marrow transplantation. High-dose chemotherapy using high-dose etoposide as therapy for relapsed germ cell tumors was associated with a 2.6% risk of developing a secondary myeloid leukemia. This figure was not significantly different from the expected rate of secondary leukemias when patients receive additional cycles of standard-dose etoposide as salvage chemotherapy for germ cell tumors. Other factors, including the use of platinum agents, may also have a role in leukemogenesis in this patient population.

Residual Masses Post Chemotherapy in Germ Cell Tumors: Role of Fluorodeoxyglucose Positron Emission Tomography Scans

Background: The standard treatment for patients with advanced germ cell tumor is 3–4 cycles of chemotherapy. Post therapy a significant number of patients have residual radiographic abnormalities. Resection of this mass depends on the histology. Those patients with viable cancer will require additional chemotherapy. An imaging study that may identify viable cancer in residual tumor is being evaluated with a Fluro-2-deoxy-D-glucose positron emission tomography (FDG PET) scan. Methods: Thirteen patients with metastatic germ cell tumors who were treated with chemotherapy who had residual abnormalities on CT scan were evaluable. They underwent a PET scan and had surgical resection. The pathological specimens were correlated with the findings on the PET scan. Results: Five patients had a positive PET scan, and eight had no uptake on a PET scan. Ten patients had pathological tissue available for correlation. The overall sensitivity and specificity of a PET scan in evaluating residual masses were 62 and 100%, respectively. Conclusion: PET imaging has limited utility in the management of patients with residual germ cell tumors.