Chemotherapy For Germ Cell Tumors Research Articles

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease.

Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.

Serum Levels of MicroRNA-371a-3p for Predicting the Histology of Postchemotherapy Residual Masses of Germ Cell Tumours

Background and objectiveSerum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment. MethodsA multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test. Key findings and limitationsThe sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation. Conclusions and clinical implicationsThe M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery. Patient summaryThe microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.

Salvage high-dose chemotherapy (HDCT) for relapsed primary mediastinal nonseminomatous germ-cell tumors (PMNSGCT).

5032 Background: Patients with PMNSGCT have high relapse rates after first-line therapy. Historical outcomes in this subset with standard-dose salvage chemotherapy or HDCT+bone marrow transplant (BMT) have been poor. The use of peripheral-blood stem-cell transplant (PBSCT) has allowed for more rapid engraftment and the ability to start the 2nd course 3-4 weeks after the 1st course of HDCT. We report survival outcomes of salvage HDCT+PBSCT in relapsed PMNSGCT. Methods: Between 2004-January 2021, 32 pts with relapsed PMNSGCT were treated with HDCT+PBSCTx2 utilizing our institutional regimen: carboplatin 700 mg/m2 + etoposide 750 mg/m2, for 3 consecutive days, followed by PBSCT. Median time between cycle1 day1 to cycle2 day1 was 3.2 wks (range, 2.6-4.6). Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) analysis. Results: Median age was 30. At the start of HDCT, median AFP was 192 (range, 4-17130) and hCG 1.5 (range, 0.6-15711). First-line therapy was standard germ cell tumor chemotherapy such as bleomycin-etoposide-cisplatin (BEP) or etoposide-ifosfamide-cisplatin (VIP). HDCT was 2nd line in (26, 81.3%) and 3rd line in (6, 18.8%). Eighteen (56.3%) pts had platinum-refractory disease defined as progression within 4 weeks of 1st line chemo. Twenty-three (72%) patients had extra mediastinal metastases (mets) at the start of HDCT. Metastatic sites included pulmonary (17), lymph nodes (2), liver (3), bone (2), brain (1). Median follow-up time from start of HDCT was 1 yr (range, 0.02-14.1). Twenty-six (81%) pts completed both cycles, while 6 (19%) completed only one cycle due to toxicity or progression. The estimated 2-yr PFS was 30.7 (95% CI, 15.8-46.9) and 2-yr OS was 35.2 (95% CI, 18.9-51.9). At the most recent follow-up, 9 (28%) pts were continuously no evidence of disease (NED), including 2 pts who had surgical resection of teratoma following HDCT. Median follow-up from the start of HDCT for the NED pts was 4.6 yrs (range, 1-14.1). Five of the NED pts had extra mediastinal mets, and 2 had platinum-refractory disease. Among the 9 NED pts, HDCT was 2nd line in 7 (77.8%) and 3rd line in 2 (22.2%). These results compare favorably to historical data with standard-dose chemotherapy or HDCT+BMT in relapsed primary mediastinal GCT with salvage rates &lt; 10% (Hartmann et al., JCO 19:1641-1648, 2001). Grade ≥3 toxicity, as previously described in our study (Adra et al., JCO 35:1096-1102, 2017), occurred in 8 (25%) pts. There were two treatment-related deaths. Conclusions: HDCT+PBSCT is a safe and effective salvage therapy in pts with relapsed PMNSGCT with curative potential. In our opinion, these complicated patients are best managed at tertiary centers with expertise in medical oncology, stem cell transplantation, and thoracic surgical oncology.

PEDT-3

Background: Germ cell tumors (GCTs) containing a teratoma component is a group of diseases consisting of various pathological conditions such as mature teratoma, immature teratoma, teratoma with malignant transformation, and mixed tumor with other GCTs. There is controversy about the efficacy and safety of radiation and chemotherapy for GCTs with teratoma component other than mature teratomas. Methods: Of 212 cases of GCTs treated at Tohoku University Hospital Neurosurgery from January 1990 to March 2021. In this study, 23 histologically verified GCTs containing teratoma components were included. Pathological findings, recurrence, survival, and late complications were examined. Results: The age of onset was 2 months-21 years (median 10.5 years). Histological diagnosis was mature teratoma alone in 5 cases, mixed GCTs with mature teratoma in 11 cases, immature teratoma in 5 cases, and mixed tumor with mature teratoma and germinoma in 2 cases. Patients except mature teratoma were treated by chemotherapy alone or radiochemotherapy. During follow-up for 7–362 months (median 135 months), 3 patients relapsed. One of these patients was diagnosed with mature teratoma at the time of treatment and did not receive post-treatment, but relapsed as germinoma 21 years later. A review of pathological specimens at the time of initial onset revealed immature teratomas in addition to mature teratomas. Recurrent lesions in 3 cases were controlled by additional treatment, and no deaths due to tumor progression were observed. On the other hand, of the 18 patients who underwent radiochemotherapy, 1 developed primary hypothyroidism and 2 developed thyroid cancer and leukemia. Conclusion: GCTs with teratoma component often contain malignant histological types and require caution when making a pathological diagnosis. In these cases, tumor control can be expected by radiation or chemotherapy, but there is a risk of developing endocrine disorders and secondary tumors, and further studies are needed to optimize treatment.

The use of granulocytic colony stimulating factors in patients receiving chemotherapy for germ cell tumors

Germ cell tumors (GCT) are a relatively rare malignancy occurring in adolescent/young males in the vast majority of cases. With the advent of platinum containing regimens 4 decades ago, impressive cure rates have been achieved both in the adjuvant setting and in first line for advanced disease, with the vast majority of patients being … Continued

Primary Mediastinal Germ Cell Tumors-The University of Western Ontario Experience.

Extragonadal germ cell tumors account for 2–5.7% of germ cell tumors (GCTs). Of these, primary mediastinal GCTs (PMGCTs) are responsible for 16–36% of cases. Given the rarity of these tumors, specific treatment strategies have not been well defined. We report our experience in treating these complex patients. In total, 318 men treated at our institution with chemotherapy for GCTs between 1980 and 2016 were reviewed. PMGCT was defined as clinically diagnosed mediastinal GCT with no evidence of testicular GCT (physical exam/ultrasound). We identified nine patients diagnosed with PMGCT. All patients presented with an anterior mediastinal mass and no gonadal lesion; four patients also had metastatic disease. Median age at diagnosis was 30 years (range, 14–56) and median mass size at diagnosis was 9 cm (range, 3.4–19). Eight patients had non-seminoma and one had pure seminoma. All patients received cisplatin-based chemotherapy initially. Surgical resection was performed in four patients; three patients had a complete resection and one patient was found to have an unresectable tumor. At a median follow-up of 2 years (range, 3 months–28 years) six patients had progressed. Progression-free survival was short with a median of 4.1 months from diagnosis (range 1.5–122.2 months). Five patients died at a median of 4.4 months from diagnosis. One and 5-year overall survivals were 50% and 38%, respectively. PMGCT are rare and aggressive. Our real-life Canadian experience is consistent with current literature suggesting that non-seminoma PMGCT has a poor prognosis despite prompt cisplatin-based chemotherapy followed by aggressive thoracic surgery.

Management of residual disease after chemotherapy in germ cell tumors.

Although testicular cancer remains a highly curable malignancy, challenges and uncertainty still remain in certain aspects of management. Residual disease after chemotherapy in patients with germ cell tumors (GCT) remains one of these challenges. We aim to highlight the recent literature on the management of residual disease after chemotherapy in GCT and the emerging innovations that may provide further guidance into this area. A subset of patients with GCT will have residual disease after chemotherapy, and management of these patients involves highly skilled multidisciplinary experts including medical oncologists, surgeons, radiologists, and pathologists. Management options depend on histologic subtype, either seminoma or nonseminoma, and involve size criteria, possible further imaging modalities, and tumor markers. Even with these tools at highly specialized expert centers, uncertainty in management remains, and recent literature has explored the use of newer biomarkers to aid in these cases. Postchemotherapy residual masses in GCT can prove to be complicated cases to manage. Balancing survival with quality of life outcomes is important and requires a multidisciplinary team experienced in treating GCT.

Less nephrotoxicity of paclitaxel and ifosfamide plus nedaplatin for refractory or relapsed germ cell tumors in patients with impaired renal function.

To determine the safety and efficacy of the combined regimen of paclitaxel and ifosfamide plus nedaplatin for patients with refractory or relapsed germ cell tumors and impaired renal function. Of a total of 68 patients who received paclitaxel, ifosfamide and nedaplatin chemotherapy for germ cell tumors, those with an estimated glomerular filtration rate <60mL/min/1.73m2 before paclitaxel, ifosfamide and nedaplatin treatment were defined as having renal dysfunction. The combination chemotherapy regimen included paclitaxel (210mg/m2 on day1) and ifosfamide (1.2g/m2 on days2-6) with nedaplatin (100mg/m2 on day2) on a 3-week cycle. A total of 10 patients had renal dysfunction with a median estimated glomerular filtration rate of 49.97mg/mL/1.73m2 (range 31.7-57.5mg/mL/1.73m2 ). Paclitaxel, ifosfamide and nedaplatin chemotherapy was given as second-line therapy in four patients, third-line in four and fourth-line or later in two. Patients with impaired renal function received pretreatment of a median of 5.5 cycles of platinum-based chemotherapy (range 3-11 cycles) with a median cisplatin dose of 550mg/m2 . The patients were given two to six cycles of paclitaxel, ifosfamide and nedaplatin chemotherapy with no dose reduction, with an overall response rate of 60%. Chemotherapy-induced kidney dysfunction was not observed in any patient with decreased renal function. Furthermore, there was no difference in the frequency of adverse events between patients with renal dysfunction (estimated glomerular filtration rate <60mL/min/1.73m2 ) and those with normal renal function (estimated glomerular filtration rate ≥60mL/min/1.73m2 ). Paclitaxel, ifosfamide and nedaplatin chemotherapy can be considered a safe and effective regimen that results in less nephrotoxicity in germ cell tumor patients with renal dysfunction.

High-dose chemotherapy in germ cell tumors: an old story still young.

Germ cell tumours represent a model of curable solid tumours. In stage 1 and 2 more than 90% the patients can achieve cure, while in advanced cases such a goal is achieved in 70-80%. For metastatic cases the standard treatment has been for more than three decades the combination of cisplatin, etoposide and bleomycin (PEB) for three or four courses depending on the prognostic category (good or intermediate/poor). Surgery on the residuum is a fundamental part of the whole program, especially in non seminoma and all efforts have to be undertaken to remove residual disease. But despite these good results, a not negligible minority of patients do relapse usually in the first one or two years. Cure can still be achieved with second line chemotherapy in 25-40% of the patients, depending on type of relapse

Pirfenidone as salvage treatment for refractory bleomycin-induced lung injury: a case report of seminoma

BackgroundBleomycin-induced lung injury, a major complication of chemotherapy for germ cell tumors, occasionally fails to respond to the standard treatment with corticosteroids and develops into severe respiratory insufficiency. Little is known about salvage treatment for refractory cases.Case presentationA 63-year-old man who had been diagnosed with stage I seminoma and undergone a high orchiectomy 1 year previously developed swelling of his left iliac lymph node and was diagnosed with a recurrence of the seminoma. He was administered a standard chemotherapy regimen of cisplatin, etoposide, and bleomycin. At the end of second cycle, he developed a dry cough and fever that was accompanied by newly-identified bilateral infiltrates on chest X-ray. Despite initiation of oral prednisolone, his exertional dyspnea and decline in pulmonary functions continued to be aggravated. High-dose pulse treatment with methylprednisolone was introduced and improved his symptoms and radiologic findings. However, the maintenance dose of oral prednisolone allowed reactivation of the disease with evidence of newly-developed bilateral lung opacities on high-resolution CT scans. Considering his glucose intolerance and cataracts as complications of corticosteroid treatment, administration of pirfenidone was initiated with the patient’s consent. Pirfenidone at 1800 mg/day was well tolerated, and resolved his symptoms and abnormal opacities on a chest CT scan. Subsequently, the dose of prednisolone was gradually tapered without worsening of the disease. At the most recent follow-up, he was still in complete remission of seminoma with a successfully tapered combination dose of prednisolone and pirfenidone.ConclusionsPirfenidone, a novel oral agent with anti-inflammatory and -fibrotic properties, should be considered as a salvage drug for refractory cases of bleomycin-induced lung injury.

A randomized phase III study of 72 h infusional versus bolus bleomycin in BEP (bleomycin, etoposide and cisplatin) chemotherapy to treat IGCCCG good prognosis metastatic germ cell tumours (TE-3)

Bleomycin is an integral part of combination chemotherapy in germ cell tumours. Pulmonary toxicity often necessitates drug cessation and death occurs in 1%-2% of patients. A continuous infusion of bleomycin might reduce lung toxicity when compared with the conventional weekly boluses given as part of standard BEP chemotherapy. A phase 3 trial was conducted based on 212 men with IGCCCG good prognosis metastatic germ cell tumours with 1:1 randomization. They were stratified for age, smoking history and renal function. Patients received either conventional BEP with weekly bleomycin (30000 units/week i.v. bolus) or as a 90000 unit infusion on day 1 over 72 h. The primary endpoint was CT assessed lung toxicity, secondary endpoints included progression-free survival (PFS), changes in lung function testing and quality of life. Repeated measures mixed effects model was used to analyse the data. CT assessed lung toxicity for the infusional and conventional arm patients were respectively 80% versus 62% at the end of treatment and 54% versus 51% at 1-year post-treatment. There was no significant difference between the two arms for CT assessed lung toxicity (estimated regression coefficient = 1.4, 95% CI: -0.36, 3.16). Older patients had higher toxicity (coefficient = 4.81, 95% CI: 3.04, 6.58). Lung toxicity increased after 1 cycle and peaked at end of treatment (P ≤ 0.002) and then declined. Lung function testing did not predict for subsequent lung damage. The median follow-up was 2.5 years. Two-year PFS rate (infusional: 93%, conventional: 94%; hazard ratio =0.91, 95% CI: 0.33, 2.52) was similar. Cough (P = 0.002) but not shortness of breath (P ≥ 0.09) was associated with bleomycin toxicity. Infusional bleomycin has no advantage over standard administration. It supports abandoning routine pulmonary function testing, instead the presence of cough should be sought and the early use of CT scanning of the chest to evaluate potential lung toxicity is preferred.

Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours

BackgroundPatients with germ cell tumours (GCT) receiving cisplatin-based chemotherapy are at high risk of thromboembolic events (TEE). Previously, we identified serum lactate dehydrogenase (LDH) and body surface area (BSA) as independent predictive factors for TEE.The aim of this study was to validate these predictive factors and to assess the impact of thromboembolism prophylaxis in patients at risk of deep venous thrombosis (DVT). MethodsBetween 2001 and 2014, 295 patients received first-line cisplatin-based chemotherapy for GCT. Preventive anticoagulation with low-molecular-weight heparin (LMWH) was progressively implemented in patients with predictive factors. Sixteen patients with evidence of TEE before starting chemotherapy were excluded from the analysis. ResultsAmong 279 eligible patients, a TEE occurred in 38 (14%) consisting of DVT (n = 26), arterial thrombosis (n = 2), and superficial thrombophlebitis (n = 10). DVT occurred in 26 (12.7%) of 204 patients with risk factors versus two (2.6%) of 75 patients with no risk factors (p = 0.01).After a prevention protocol was progressively implemented from 2005, primary thromboprophylaxis was administered to 104 patients (68%) with risk factors. Among patients at risk (n = 151), the incidence of DVT decreased by roughly half when they received a LMWH: 9/97 (9.2%) and 9/54 (16.6%), respectively (p = 0.23). ConclusionPatients with GCT who receive cisplatin-based chemotherapy are at risk of developing a TEE which can be predicted by elevated serum LDH. To our knowledge this is the first study exploring LMWH as thromboprophylaxis in GCT patients. A prospective trial testing prophylactic anticoagulation is warranted.

A Case of Langerhans Cell Histiocytosis Manifested as a Suprasellar Mass.

Langerhans cell histiocytosis (LCH) has diverse clinical manifestations, including intracranial mass lesions. We report a case of LCH that manifested as a suprasellar mass, and initially misdiagnosed as a germ cell tumor. A 29-year-old woman presented with polyuria, polydipsia and amenorrhea. Laboratory findings revealed hypopituitarism with central diabetes insipidus, and a suprasellar mass and a pineal mass were observed on magnetic resonance imaging. Under the clinical impression of a germ cell tumor, the patient was treated with germ cell tumor chemotherapy (cisplatin and etoposide) and radiation therapy without biopsy. After initial shrinkage of the lesions, further growth of the tumor was observed and a biopsy was performed. The histopathology revealed LCH. After chemotherapy according to the LCH III protocol, the tumor disappeared. She is on regular follow up for 5 years without relapse. The present findings indicate that LCH should be included in the differential diagnosis of a suprasellar mass, even in adults, especially when it manifests with diabetes insipidus. This case also underscores the importance of a histopathologic diagnosis in patients with suprasellar tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive of a specific diagnosis.

2599 Gemcitabine, Cisplatin, and Paclitaxel (GCT) as second-line salvage chemotherapy for germ cell tumors

2599 Gemcitabine, Cisplatin, and Paclitaxel (GCT) as second-line salvage chemotherapy for germ cell tumors

High-dose chemotherapy with autologous stem cell transplantation in relapsed or refractory germ cell tumours: outcomes and prognostic variables in a case series of 17 patients.

Optimal therapy for men relapsing after initial chemotherapy for germ cell tumours (GCT) is poorly defined. Both conventional dose salvage regimens and high-dose chemotherapy with autologous stem cell transplantation (HDCT-ASCT) have been utilised. To examine patients who received HDCT-ASCT for relapsed GCT within a single Australian centre. Records between 2000 and 2012 were analysed for baseline characteristics, treatment-related toxicity and survival. Prognosis at the time of HDCT-ASCT was classified according to the International Prognostic Factors Study Group (IPFSG). Seventeen patients received HDCT-ASCT, median age 34 (21-46), with 41% having primary refractory disease and 53% with high/very high risk disease by IPFSG. The most common regimen utilised was paclitaxel/ifosfamide followed by high-dose carboplatin/etoposide (TI-CE; n = 12). The median duration of grade 4 (G4) neutropenia was 11 days (range 9-17) with febrile neutropenia in 90% resulting in four intensive care unit admissions (8%). Median duration of G4 thrombocytopenia was 10 days (range 8-19) requiring a median of two pooled platelets bags (range 0-33) per episode. Transplant-related mortality occurred in one patient (veno-occlusive disease). Twenty-seven per cent of HDCT-ASCT cycles were associated with grade 3 mucositis (median total parenteral nutrition days = 5 (0-23)). Two-year progression-free survival (PFS) and overall survival (OS) rates were 59% and 71%. Patients who received HDCT-ASCT as second or subsequent relapse fared worse than those treated with HDCT-ASCT at first relapse (hazard ratio 0.23 (95% confidence interval: 0.04, 1.37; P-value 0.09). Three-year OS for those who received TI-CE at first relapse was 90%. HDCT-ASCT for relapsed GCT is effective with acceptable toxicity. There was encouraging PFS/OS, particularly in a poor-prognosis cohort.

Paclitaxel, ifosfamide, and cisplatin (TIP) as salvage and consolidation chemotherapy for advanced germ cell tumor.

Purpose The purpose of the study was to assess the efficacy of TIP as salvage chemotherapy for germ cell tumor (GCT) patients with relapsed disease or cisplatin (CDDP)-refractory disease and consolidation chemotherapy for patients who responded unfavorably to first-line chemotherapy.MethodsForty-three patients with advanced GCT were treated with TIP. Eleven with relapsed disease and five with CDDP-refractory disease received TIP as salvage chemotherapy. The remaining 27 received TIP as consolidation chemotherapy following initial induction chemotherapy. All patients received prophylactic granulocyte colony-stimulating factor.ResultsIn total, 116 cycles of TIP were administered with a median of three cycles (range 1–4 cycles) per patient. Before TIP, 33 patients showed elevated tumor marker and 23 patients (70 %) achieved marker normalization with the chemotherapy. One of six (17 %) patients with refractory disease and 5 of 10 (50 %) patients with relapsed disease achieved durable complete response (CR) after TIP with or without surgery. Eighteen of 27 (67 %) patients receiving TIP as consolidation chemotherapy achieved durable CR. Five additional patients were given further chemotherapy and achieved durable CR. Grade 4 leukocytopenia and thrombocytopenia were observed in 91 and 42 % of patients, respectively; all were managed with routine supportive care. Grade 2 and grade 3 sensory neuropathy was observed in 37 and 2 % of patients, respectively.ConclusionsThe TIP was effective for relapsed patients with favorable risk features and selected CDDP-refractory GCT patients. Results of TIP as consolidation for patients with unfavorable response to the initial chemotherapy were also encouraging. The toxicities were mainly myelosuppression and sensory neuropathy.

Results of a 7-day aprepitant schedule for the prevention of nausea and vomiting in 5-day cisplatin-based germ cell tumor chemotherapy

The purpose of this study was to determine the efficacy of adding a 7-day aprepitant schedule to a 5HT3 receptor antagonist and dexamethasone for patients with germ cell tumors receiving first-line 5-day cisplatin-based chemotherapy. In a single-arm, open-label, multi-center, phase 2 trial, chemo-naive patients received aprepitant 125 mg PO (per oral) on day 1 and 80 mg PO on days 2 to 7, a 5HT3 receptor antagonist on days 1 to 5, and dexamethasone 8 mg on days 1 to 8. The primary endpoint was no emesis (vomiting or dry retching) during days 1 to 7 of cycle 1. Fifty patients were recruited. For cycle 1, proportions reporting no emesis on day 1, no emesis on days 1 to 7, no nausea on day 1, and no nausea on days 1 to 7 were 96, 82, 71, and 27%, respectively. The efficacy was maintained in all cycles with over 80% of patients reporting no emesis on any given day of any given cycle. Emesis was more common on days 4 to 7 (68% episodes) than on days 1 to 3 (32% episodes). Over any 24-h period, 49% of patients with emesis reported no more than two episodes, and 62% of patients with nausea reported intensity as 3 or less on a scale from 0 to 10. There were no unexpected or serious adverse events reported. Adding 7 days of aprepitant to a 5HT3 receptor antagonist and dexamethasone effectively controlled acute and delayed emesis with 5-day cisplatin regimens. Days of nausea were more common than days of vomiting.

Teratoma with somatic-type malignant components of the testis. A review and an update

Malignant transformation of germ cell tumors into somatic malignancy is uncommon. Its presentation differs from series to series, with 43 % of adult cases identified within the primary tumors and the remainder at the time of relapse or in the metastasis. Patients with stage I disease enjoy an excellent prognosis; whereas in metastatic sites when not completely resectable, the somatic type malignancies suffer a dismal prognosis. Radical surgery is significant for the prospects of cure and is standard chemotherapy for germ cell tumors; a transformation-oriented treatment can be effective for these patients. A deeper understanding of the biology of this phenomenon is essential for clinicians involved in such malignancies in order to permit a better control of the disease.

Comparison of standard versus high dose of paclitaxel with ifosfamide and cisplatin (TIP) in salvage therapy of germ cell tumors (GCTs).

e15028 Background: Currently, TIP with higher dose of paclitaxel (250mg/m2) is considered standard salvage chemotherapy in GCTs with good prognostic features. However, until 2007, we utilized regimen with standard dose of paclitaxel (175mg/m2). The aim of this study was to compare the efficacy of TIP with the standard versus higher dose of paclitaxel as first salvage therapy for patients with relapsed GCTs. Methods: This retrospective study included 64 patients with relapsed GCTs treated with TIP as first salvage therapy between 1998 and 2010 in two major cancer centers in Slovakia. Forty five patients (70%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen). Four cycles of standard dose (175mg/m2, 37 patients) or higher dose (250 mg/m2, 27 patients) of paclitaxel (day 1) with ifosfamide 1.2 g/m2 (day 1-5) and cisplatin 20 mg/m2 (day 1-5) were given 21 days apart with G-CSF support, followed by resection of resectable radiographic residua. Results: Nineteen of 37 (51%) patients treated with standard dose of paclitaxel achieved favourable response (complete remission or partial remission with negative serum tumor markers) compared to 20 of 27 (74%) patients treated with higher dose of paclitaxel (p = 0.07). In median follow-up of 23.9 months 37 patients (58%) experienced disease relapse and 33 (52%) patients died. Patients treated with higher dose of paclitaxel had better progression-free survival (median: not reached vs. 7 months, HR = 0.54, 0.28 - 1.04; p = 0.06) and overall survival (median: not reached vs. 33 months, HR = 0.69, 0.34-1.39; p = 0.31) compared to patients treated with standard dose of paclitaxel. Conclusions: Our data support the hypothesis that higher dose of paclitaxel with ifosfamide and cisplatin is associated with better outcome compared to standard dose of paclitaxel in patients with relapsed GCTs treated in first relapse.

Late Cardiovascular Toxicity Following Chemotherapy for Germ Cell Tumors

The introduction of cisplatin-based chemotherapy has transformed germ cell tumors (GCTs), the most common malignancy to affect young adult men, into a highly curable cancer, even in the setting of advanced disease. However, over the past decade, the success of these chemotherapy regimens in curing GCTs has been temporized by an increasing recognition of their important late toxicities, such as cardiovascular disease. The relative risk of coronary artery disease in this population is particularly elevated within the first 10 years of follow-up, when patients are still in their 30s and 40s, which are age groups often considered too young to experience cardiovascular events. Two hypotheses have been proposed to explain the association between chemotherapy and cardiovascular disease in this population. The direct hypothesis asserts that chemotherapy causes diffuse endothelial damage, including in the coronary arteries, gradually leading to cardiovascular disease. In contrast, the indirect hypothesis proposes that chemotherapy leads to an increased incidence of cardiovascular disease risk factors, such as hypertension, hyperlipidemia, and the metabolic syndrome, which in turn enhance the risk of cardiovascular disease. This article summarizes the data on the association between chemotherapy (predominantly cisplatin-based) and the development of cardiovascular disease among GCT survivors, and reviews the evidence supporting both mechanistic hypotheses. In addition, recommendations are provided for the management of GCT survivors who received cisplatin-based chemotherapy and are therefore at risk for cardiovascular toxicity.