Gonzalez-Billalabeitia, E., J. M. Sepulveda, P. Maroto, et al. 2016. "Consensus Recommendations from the Spanish Germ Cell Cancer Group on the Use of High-dose Chemotherapy in Germ Cell Cancer." Eur Urol Focus.
BACKGROUND:High-dose chemotherapy (HDCT) has been studied in several clinical scenarios in advanced germ cell cancer (GCC).
OBJECTIVE:To establish a clinical practice guideline for HDCT use in the treatment of GCC patients.
DESIGN, SETTING, AND PARTICIPANTS:An expert panel reviewed information available from the literature. The panel addressed relevant issues concerning and related to HDCT. The guideline was externally reviewed by two international experts.
RESULTS AND LIMITATIONS:The efficacy of HDCT has been demonstrated in selected GCC patients. The most conclusive evidence comes from retrospective analyses that need to be interpreted with caution. HDCT can cure a significant proportion of heavily treated GCC patients. When indicated, sequential HDCT with regimens containing carboplatin and etoposide, as well as peripheral stem-cell support, is recommended. There is no conclusive evidence to recommend HDCT as first-line therapy. According to a multinational retrospective pooled analysis, HDCT might be superior to conventional CT as first salvage treatment in selected patients. There is an urgent need for prospective clinical trials addressing the value of HDCT in GCC patients who experience failure on first-line cisplatin-based CT. In patients who progress on conventional-dose salvage CT, HDCT should be considered. Treatment of these patients at experienced centers is strongly recommended.
CONCLUSIONS:It has been demonstrated that HDCT cures selected GCC patients who experience disease progression on conventional rescue regimens. The panel recommends the inclusion of GCC patients in randomized clinical trials including HDCT.
PATIENT SUMMARY:This consensus establishes clinical practice guidelines for the use and study of high-dose chemotherapy in patients with germ cell cancer.
Motzer, R. J., C. J. Nichols, K. A. Margolin, et al. 2007. "Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors." J Clin Oncol 25(3):247-256.
PURPOSE: To investigate the role of high-dose chemotherapy (HDCT) as first-line treatment in patients with metastatic germ cell tumor (GCT) and poor-prognostic clinical features. Serum tumor marker decline during chemotherapy was assessed prospectively as a predictor of treatment outcome. PATIENTS AND METHODS: In this randomized phase III trial, previously untreated patients with intermediate- or poor-risk GCT received either four cycles of standard bleomycin, etoposide, and cisplatin (BEP alone), or two cycles of BEP followed by two cycles of HDCT containing carboplatin and then by hematopoietic stem-cell rescue (BEP + HDCT). Serum tumor markers alpha-fetoprotein and human chorionic gonadotrophin were correlated with treatment outcome as a secondary end point. RESULTS: Two hundred nineteen patients were randomly assigned: 108 to BEP + HDCT and 111 to BEP alone. The 1-year durable complete response rate was 52% after BEP + HDCT and 48% after BEP alone (P = .53). Patients with slow serum tumor marker decline (alpha-fetoprotein and/or human chorionic gonadotrophin) during the first two cycles of chemotherapy had a shorter progression-free survival and overall survival compared with patients with satisfactory marker decline (P = .02 and P = .03, respectively). Among 67 patients with unsatisfactory marker decline, the 1-year durable complete response proportion was 61% for patients who received HDCT versus 34% for patients receiving BEP alone (P = .03). CONCLUSION: The routine inclusion of HDCT in first-line treatment for GCT patients with metastases and a poor predicted outcome to chemotherapy did not improve treatment outcome. Frequent serum marker determinations to estimate marker decline during the first two cycles of BEP chemotherapy provide a clinically useful estimate of outcome.
Einhorn LH, Williams SD, Chamness A et al. 2007 " High-dose chemotherapy and stem-cell rescue for metastatic germ-cell tumors". N Engl J Med. Jul 26;357(4):340-8.
BACKGROUND : Metastatic testicular tumors that have not been successfully treated by means of initial chemotherapy are potentially curable with salvage chemotherapy. METHODS : We conducted a retrospective review of 184 consecutive patients with metastatic testicular cancer that had progressed after they received cisplatin-containing combination chemotherapy. We gave 173 patients two consecutive courses of high-dose chemotherapy consisting of 700 mg of carboplatin per square meter of body-surface area and 750 mg of etoposide per square meter, each for 3 consecutive days, and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells; the other 11 patients received a single course of this treatment. In 110 patients, cytoreduction with one or two courses of vinblastine plus ifosfamide plus cisplatin preceded the high-dose chemotherapy. RESULTS : Of the 184 patients, 116 had complete remission of disease without relapse during a median follow-up of 48 months (range, 14 to 118). Of the 135 patients who received the treatment as second-line therapy, 94 were disease-free during follow-up; 22 of 49 patients who received treatment as third-line or later therapy were disease-free. Of 40 patients with cancer that was refractory to standard-dose platinum, 18 were disease-free. A total of 98 of 144 patients who had platinum-sensitive disease were disease-free, and 26 of 35 patients with seminoma and 90 of 149 patients with nonseminomatous germ-cell tumors were disease-free. Among the 184 patients, there were three drug-related deaths during therapy. Acute leukemia developed in three additional patients after therapy. CONCLUSIONS : Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem-cell rescue, even when this regimen is used as third-line or later therapy or in patients with platinum-refractory disease.
Kondagunta GV, Bacik J, Sheinfeld J et al. 2007 "Paclitaxel plus Ifosfamide followed by high-dose carboplatin plus etoposide in previously treated germ cell tumors". J Clin Oncol. Jan 1;25(1):85-90.
PURPOSE: To evaluate the optimal dose of carboplatin as well as the efficacy and tolerability of sequential, dose-intense chemotherapy with paclitaxel and ifosfamide followed by carboplatin and etoposide (TICE) plus peripheral-blood stem-cell (PBSC) support in patients with germ cell tumors (GCT) who are likely to experience treatment failure with conventional-dose salvage treatment. This prospective trial followed a similarly designed report of TICE, which used a different means of carboplatin dosing. PATIENTS AND METHODS: The 48 patients entered onto this trial had progressive GCT and unfavorable prognostic features after chemotherapy. Two cycles of paclitaxel plus ifosfamide were administered with leukapheresis, followed by three cycles of carboplatin plus etoposide with reinfusion of PBSC. RESULTS: Twenty-three (49%) of 47 assessable patients achieved a complete response (CR) to chemotherapy. An additional three patients (6%) achieved a CR to chemotherapy and surgery. The CR rate was 55%. Six patients experienced relapse, but 24 patients (51%) are alive and free of disease at a median follow-up time of 40 months. Four patients who experienced relapse or achieved an incomplete response were rendered disease free by salvage surgical resection. When combined with results of the prior trial of similar design, TICE chemotherapy yielded an overall CR of 56% (n = 84), with 50% of patients alive with no evidence of disease. CONCLUSION: TICE is an effective and tolerable dose-intense treatment for patients with previously treated metastatic GCT who have a poor predicted outcome to conventional-dose salvage chemotherapy.
Lorch A, Bascoul-Mollevi C, Kramar A et al. 2011 Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database. J Clin Oncol. Jun 1;29(16):2178-84
PURPOSE : Conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) may both be successfully used as salvage treatment for patients with metastatic germ cell tumors (GCTs) who experience progression with first-line treatment. PATIENTS AND METHODS : Data on 1,984 patients with GCTs who experienced progression after at least three cisplatin-based cycles and were treated with either cisplatin-based CDCT or carboplatin-based HDCT chemotherapy were collected from 38 centers or groups worldwide. Of 1,984 patients, 1,594 (80%) were eligible, and among the eligible patients, 1,435 (90%) could reliably be classified into one of the following five prognostic categories based on prior prognostic classification: very low (n = 76), low (n = 257), intermediate (n = 646), high (n = 351), and very high risk (n = 105). Within each of the five categories, the progression-free survival (PFS) and overall survival (OS) after CDCT and HDCT were compared using the Cox model adjusted for significant distributional differences between important variables. RESULTS : Overall, 773 patients received CDCT, and 821 patients received HDCT. Both treatment modalities were used with similar frequencies within each prognostic category. The hazard ratio for PFS was 0.44 (95% CI, 0.39 to 0.51) stratified on prognostic category, and the hazard ratio for OS was 0.65 (95% CI, 0.56 to 0.75), favoring HDCT. These results were consistent within each prognostic category except among low-risk patients, for whom similar OS was observed between the two treatment groups. CONCLUSION: This retrospective analysis suggests a benefit from HDCT given as intensification of first salvage treatment in male patients with GCTs and emphasizes the need for another prospective randomized trial comparing CDCT to HDCT in this patient population
Pico JL, Rosti G, Kramar A et al. 2005 A randomised trial of high-dose chemotherapy in the salvage treatment of patients failing first-line platinum chemotherapy for advanced germ cell tumours.Ann Oncol. 2005 Jul;16(7):1152-9
BACKGROUND : Incomplete remission or relapse from first-line chemotherapy has poor prognosis in male germ cell tumour patients. This phase III randomised trial compares conventional salvage to high-dose-intensification chemotherapy. PATIENTS AND METHODS : Between February 1994 and September 2001, 280 patients from 43 institutions in 11 countries, were randomly assigned to receive either four cycles of cisplatin, ifosfamide and etoposide (or vinblastine) (arm A), or three such cycles followed by high-dose carboplatin, etoposide and cyclophosphamide (CarboPEC) with haematopoietic stem cell support (arm B). RESULTS: Similar complete and partial response rates were observed in both treatment arms (56%; 95% CI 50% to 62%). There were 3% and 7% toxic deaths in arms A and B, respectively. No significant improvements with CarboPEC were observed in either 3-year event-free survival (35% versus 42%, P=0.16) or overall survival (53%; 95% CI 46% to 59%). Complete responders with CarboPEC had a significant improvement in disease-free survival (55% versus 75% at 3 years, P <0.04). CONCLUSIONS : The single cycle of high-dose salvage chemotherapy after three cycles of standard dose chemotherapy had no effect on treatment outcomes. These results suggest that data from uncontrolled studies should not be used to justify routine use of a toxic and expensive treatment without confirmation in a randomised trial.
Feldman, D. R., R. Huddart, E. Hall, et al. 2011. "Is high dose therapy superior to conventional dose therapy as initial treatment for relapsed germ cell tumors? The TIGER Trial." J Cancer 2:374-377.
Metastatic germ cell tumours (GCTs) are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT) and high dose therapy (HDT) are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP) with sequential HDT (TICE). The planned open labelled randomised phase III study (TIGER) is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint). It is hoped that this large study will conclusively resolve the uncertainty which currently exists.
Feldman, D. R., J. Sheinfeld, D. F. Bajorin, et al. 2010. "TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis." J Clin Oncol 28(10):1706-1713.
PURPOSE: We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients. PATIENTS AND METHODS: Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed. RESULTS: Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models. CONCLUSION: TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.
Lorch A, Kollmannsberger C, Hartmann JT et al. 2007 " Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group ". J Clin Oncol. Jul 1;25(19):2778-84.
PURPOSE : To compare single versus sequential high-dose chemotherapy (HDCT) as first or subsequent salvage treatment in patients with relapsed or refractory germ cell tumors (GCTs). PATIENTS AND METHODS : Between November 1999 and November 2004, 230 patients were planned to be recruited in a prospective, randomized, multicenter trial comparing one cycle of 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) versus three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2, and cyclophosphamide 6,400 mg/m2 (CEC; arm B). RESULTS: The study was stopped prematurely after recruitment of 216 patients as a result of excess treatment-related mortality in arm B. One hundred eleven (51%) of 216 patients were randomly assigned to sequential HDCT, and 105 (47%) of 216 patients were randomly assigned to single HDCT. Five (2%) of 216 patients had to be excluded because of non-GCT histologies at review. With a median follow-up time of 36 months, 109 (52%) of 211 patients were alive, and 91 (43%) of 211 patients were progression free. At 1 year, event-free, progression-free, and overall survival rates were 40%, 53%, and 80%, respectively, in arm A compared with 37%, 49%, and 61%, respectively, in arm B (P > .05 for all comparisons). Treatment-related deaths, mainly as a result of sepsis and cardiac toxicity, were less frequent in arm A (four of 108 patients, 4%) compared with arm B (16 of 103 patients, 16%; P < .01). CONCLUSION : We found no difference in survival probabilities between single HDCT using CE and sequential HDCT using CEC. Sequential HDCT was better tolerated and resulted in fewer treatment-related deaths.
Rick O, Bokemeyer C, Beyer J et al. 2001. " Salvage treatment with paclitaxel, ifosfamide, and cisplatin plus high-dose carboplatin, etoposide, and thiotepa followed by autologous stem-cell rescue in patients with relapsed or refractory germ cell cancer". J Clin Oncol. ;19(1):81-8.
PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS : Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m(2), ifosfamide 5 x 1.2 g/m(2), and cisplatin 5 x 20 mg/m(2) (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m(2) x 3, etoposide 600 mg/m(2) x 4, and thiotepa 150 to 250 mg/m(2) x 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m(2) and ifosfamide 5 g/m(2) (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects.CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.
Motzer RJ, Mazumdar M, Sheinfeld J et al. " Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients". J Clin Oncol. 2000;18(6):1173-80.
PURPOSE : To evaluate the efficacy and toxicity of sequential, dose-intensified chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide administered plus peripheral blood-derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in response to conventional-dose salvage programs. Carboplatin was dose escalated by target area under the curve (AUC; in [milligrams per milliliter]x minutes) among patient cohorts, and pharmacokinetic studies were performed for comparison. PATIENTS AND METHODS : Thirty-seven previously treated patients who had cisplatin-resistant GCT and unfavorable prognostic features for response to conventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 mg/m(2) plus ifosfamide 6 g/m(2) were given 2 weeks apart with leukapheresis, followed by three cycles of carboplatin plus etoposide given 14 to 21 days apart with reinfusion of PBSCs. The dose of etoposide was 1, 200 mg/m(2), and the carboplatin target AUC ranged among cohorts from 12 to 32 (mg/mL) x min. Pharmacokinetic studies of carboplatin were performed for comparison of target to measured AUC. RESULTS: Twenty-one patients (57%) achieved a complete response and an additional two patients (5%) achieved a partial response with normal tumor markers; therefore, 23 (62%) achieved a favorable response. Eight patients relapsed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of carboplatin/etoposide cycles were associated with hospitalization for nadir fever. The AUC of carboplatin measured in serum was lower than the target AUC; this may be related to underestimation of the glomerular filtration rate used in the dosing formula. CONCLUSION : Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.
Lorch, A., A. Kleinhans, A. Kramar, et al. 2012. "Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: long-term results of a prospective randomized trial." J Clin Oncol 30(8):800-805.
PURPOSE: To evaluate the long-term survival rates in patients with relapsed or refractory germ cell tumors (GCTs) after single or sequential high-dose chemotherapy (HDCT).
PATIENTS AND METHODS: Between November 1999 and November 2004, 211 patients with relapsed or refractory GCT were randomly assigned to treatment with either one cycle of cisplatin 100 mg/m(2), etoposide 375 mg/m(2), and ifosfamide 6 g/m(2) (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m(2) and etoposide 1,500 mg/m(2) (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m(2), etoposide 1,800 mg/m(2), and cyclophosphamide 6,400 mg/m(2) (CEC, arm B) followed by autologous stem-cell reinfusion. Long-term progression-free survival (PFS) and overall survival (OS) 6 years after random assignment of the last patient were compared by using the log-rank test.
RESULTS: Overall, 108 and 103 patients were randomly assigned to arms A and B, respectivelyl. The study was stopped prematurely because of excess treatment-related mortality in arm B (14%) compared with that in arm A (4%; P = .01). As of December 2010, nine (5%) of 211 patients were lost to follow-up; 94 (45%) of 211 are alive and 88 (94%) of 94 patients are progression free. Five-year PFS is 47% (95% CI, 37% to 56%) in arm A and 45% (95% CI, 35% to 55%) in arm B (hazard ratio [HR], 1.16; 95% CI, 0.79 to 1.70; P = .454). Five-year OS is 49% (95% CI, 40% to 59%) in arm A and 39% (95% CI, 30% to 49%) in arm B (HR, 1.42; 95% CI, 0.99 to 2.05; P = .057).
CONCLUSION: Patients with relapsed or refractory GCT achieve durable long-term survival after single as well as sequential HDCT. Fewer early deaths related to toxicity translated into superior long-term OS after sequential HDCT.
Feldman, D. R. and T. Powles. 2015. "Salvage high-dose chemotherapy for germ cell tumors." Urol Oncol 33(8):355-362.
BACKGROUND: Salvage high-dose chemotherapy (HDCT) along with autologous stem cell transplant (ASCT) plays an important role in the management of patients with germ cell tumors (GCT) and progression after first-line cisplatin-based chemotherapy. In this review, the authors will discuss the history of HDCT as salvage management of patients with GCT, improvement in efficacy and safety over the past 25 years, prognostic factors for outcome, and the conflicting data on the optimal initial salvage approach. METHODS: The authors performed a PubMed search of HDCT and GCT to identify articles relevant to this review. After discussion, the articles felt to have contributed most notably to the field were selected for inclusion and summarized. RESULTS: Depending on patient selection and timing of HDCT, durable remission rates with salvage HDCT range between 30% and 63%. The combination of carboplatin and etoposide is the standard regimen for the high-dose cycles with more variability in the regimens used for stem cell mobilization. Adding a third agent, particularly an oxazophosphorine (cyclophosphamide and ifosfamide), may add toxicity without increasing efficacy. In addition, sequential (2 or 3 cycle) HDCT regimens appear more effective and safer than single-cycle HDCT regimens. The optimal initial salvage approach (HDCT or conventional-dose chemotherapy) remains an unanswered question and highly controversial. CONCLUSIONS: Salvage HDCT with ASCT can cure a significant proportion of patients with GCT and progression after one or more lines of cisplatin-based chemotherapy and thus plays an important role in the contemporary management of high-risk patients.
International Prognostic Factors Study, Group, A. Lorch, J. Beyer, et al. 2010. "Prognostic factors in patients with metastatic germ cell tumors who experienced treatment failure with cisplatin-based first-line chemotherapy." J Clin Oncol 28(33):4906-4911.
PURPOSE: To develop a prognostic model in patients with germ cell tumors (GCT) who experience treatment failure with cisplatin-based first-line chemotherapy. PATIENTS AND METHODS: Data from 1,984 patients with GCT who progressed after at least three cisplatin-based cycles and were treated with cisplatin-based conventional-dose or carboplatin-based high-dose salvage chemotherapy was retrospectively collected from 38 centers/groups worldwide. One thousand five hundred ninety-four (80%) of 1,984 eligible patients were randomly divided into a training set of 1,067 patients (67%) and a validation set of 527 patients (33%). Seminomas were set aside for posthoc analyses. Primary end point was the 2-year progression-free survival after salvage treatment. RESULTS: Overall, 990 patients (62%) relapsed and 604 patients (38%) remained relapse free. Histology, primary tumor location, response, and progression-free interval after first-line treatment, as well as levels of alpha fetoprotein, human chorionic gonadotrophin, and the presence of liver, bone, or brain metastases at salvage were identified as independent prognostic variables and used to build a prognostic model in the training set. Survival rates in the training and validation set were very similar. The estimated 2-year progression-free survival rates in patients not included in the training set was 75% in very low risk, 51% in low risk, 40% in intermediate risk, 26% in high risk, and only 6% in very high-risk patients. Due to missing values in individual variables, 69 patients could not reliably be classified into one of these categories. CONCLUSION: Prognostic variables are important in patients with GCT who experienced treatment failure with cisplatin-based first-line chemotherapy and can be used to construct a prognostic model to guide salvage strategies.
Ozaydin, S., U. Sahin, N. Karadurmus, et al. 2017. "An overview of high dose chemotherapy with autologous stem cell rescue for germ cell tumors in current practice." J BUON 22(2):306-311.
Testicular cancer is a frequent tumor of adolescent and young adult males. Chemotherapy has been reported to provide cure rates as high as 80% even in the presence of advanced testicular cancer. Studies regarding testicular cancer started after the advent of high dose chemotherapy (HDC) plus atologous stem cell rescue (ASCR) for the treatment of solid tumors in 1980s. Testicular cancer is highly responsive to HDC. Einhorn et al. have reported long-lasting remissions reaching up to 40% among patients with platinum-refractory disease. However, the present prospective randomized studies are heterogeneous in terms of patient characteristics and methodology, therefore superiority of HDC plus ASCR to conventional chemotherapies could not be proven. The results of the TIGER study, which is a recent prospective randomized study being conducted by the European Organisation for Research and Treatments in Cancer (EORTC) and the European Society for Blood and Marrow Transplantation (EBMT) aiming to compare HDC plus ASCR to conventional chemotherapy are eagerly expected. In this review, we will evaluate the current use of HDC plus ASCR in patients with relapsed or refractory germ cell tumors.