Good-risk Germ Cell Tumors Research Articles

Four Cycles of Etoposide plus Cisplatin for Patients with Good-Risk Advanced Germ Cell Tumors

BackgroundThe National Comprehensive Cancer Network recommends either three cycles of bleomycin, etoposide, and cisplatin or four cycles of etoposide and cisplatin (EPx4) as initial chemotherapy for the treatment of good‐risk germ cell tumors (GCTs). To assess the response, toxicity, and survival outcomes of EPx4, we analyzed our experience.Material and MethodsResponse and survival outcomes, selected toxicities, and adherence to chemotherapy dose and schedule were assessed in patients with good‐risk GCT who received EPx4 at Memorial Sloan Kettering Cancer Center between 1982 and 2016. The results were compared with our past results and published data.ResultsBetween 1982 and 2016, 944 patients with GCT were treated with EPx4, 289 who were previously reported plus 655 treated between January 2000 and August 2016. A favorable response was achieved in 928 of 944 patients (98.3%). Five‐year progression‐free, disease‐specific, and overall survival rates were 93.9%, 98.6%, and 97.9%, respectively. Median follow‐up was 7.3 years (range, 2.8 months to 35.5 years). Viable, nonteratomatous malignant GCT was present in 3.5% of 432 postchemotherapy retroperitoneal lymph node dissection specimens from patients with nonseminomatous GCT. Febrile neutropenia and thromboembolic events occurred in 16.0% and 8.9%, respectively, with one treatment‐related death. In the more recent 655‐patient cohort, full‐dose EPx4 was administered to 631 (96.3%), with deviations from planned treatment driven mainly by vascular (n = 13), hematologic (n = 11), renal (n = 7), or infectious (n = 5) events.ConclusionEPx4 is highly effective and well tolerated in patients with good‐risk GCTs and remains a standard of care.Implications for PracticeFour cycles of etoposide and cisplatin (EPx4) is a standard‐of‐care regimen for all patients with good‐risk germ cell tumors with a favorable response rate and disease‐specific survival of 98%. Full‐dose administration of etoposide and cisplatin and complete resection of residual disease lead to optimal outcomes. EPx4 should be the recommended regimen in active smokers, patients with reduced or borderline kidney function, and patients aged 50 years or older, which are patient groups at increased risk for bleomycin pulmonary toxicity. Because of a risk of acquired severe pulmonary illness, EPx4 may also be favored for patients who vape or use e‐cigarettes and during ongoing transmission of severe acute respiratory syndrome coronavirus 2.

Improved outcomes in testicular germ cell tumor patients treated at the referral center in Slovakia in the last decade.

e16059 Background: Treatment at expert centers results in superior survival in patients with germ cell tumors (GCTs). This study evaluated outcomes in patients treated at National Cancer Institute in Slovakia before and after the year 2008 after refining the treatment strategies. Methods: Our institutional database was searched for GCT patients treated at National Cancer Institute in Slovakia between 1992 and 2016. A year of 2008 was selected for cutoff to compare changes in outcomes before and after this time-point due to refining treatment strategies such as centralization of post-chemotherapy surgery and incorporation of granulocyte-colony stimulating factor (G-CSF) for routine prophylaxis of febrile neutropenia. Kaplan-Meier product limit and log-rank test were used for statistical analysis. Results: This retrospective study included 485 patients treated for metastatic GCT. Two hundred and sixty-three patients (54%) were treated before 2008 (group 1) and 222 patients (46%) were treated after 2008, including (group 2). Progression-free survival (PFS) and overall survival (OS) was significantly improved in group 2 vs 1 (HR = 0.63, 95% CI 0.46-0.87; P= 0.0039 for PFS and HR = 0.44, 95% CI 0.30-0.65; P = 0.0003 for OS, respectively). In a subgroup analysis of International Germ Cell Cancer Collaborative Group criteria, favorable change in survival was observed in good-risk GCTs (HR = 0.40, 95% CI 0.24-0.67; P = 0.0009 for PFS, and HR = 0.20, 95% CI 0.10-0.38; P = 0.0002 for OS), but nor in intermediate or poor risk group. Conclusions: Treatment outcomes of GCTs have significantly improved in the last decade at our institution. We hypothesize that changes in treatment approach contributed to this improvement including centralization of post-chemotherapy retroperitoneal lymph-node dissections and routine use of granulocyte-colony stimulating factors that have been implemented in 2007. Referral bias for extremely poor risk patients in recent years may be an accounting factor for lack of improvement in this subgroup.

Risk of Bleomycin-Related Pulmonary Toxicities and Operative Morbidity After Postchemotherapy Retroperitoneal Lymph Node Dissection in Patients With Good-Risk Germ Cell Tumors.

Three cycles of bleomycin, etoposide, and cisplatin (BEP × 3) or four cycles of etoposide and cisplatin (EP × 4) are first-line chemotherapy regimens for men with International Germ Cell Cancer Collaborative Group (IGCCCG) good-risk germ cell tumors (GCTs). We determined whether inclusion of bleomycin affected pulmonary and operative morbidity after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We queried our database to identify IGCCCG good-risk patients who received BEP × 3 or EP × 4 induction chemotherapy before PC-RPLND from 2006 to 2016. Patients who received combination regimens were excluded. The primary outcomes of interest were pulmonary morbidity (prolonged intubation, reintubation, supplemental oxygen use, intensive care unit stay) and operative morbidity (operative time, length of stay, concomitant procedures, estimated blood loss). We analyzed 234 patients (191 BEP × 3 v 43 EP × 4). All patients were extubated immediately after the operation. None were reintubated or discharged on oxygen. Two patients in each cohort required an intensive care unit stay for nonpulmonary reasons. Patients treated with BEP required shorter use of supplemental oxygen (0.99 v 1.63 days; P = .005). No significant differences were found in preoperative mass size ( P = .42) or concomitant surgeries ( P = .58). Operative time was significantly shorter (131 v 170 minutes; P < .01), and estimated blood loss was considerably less (194 v 226 mL; P < .01) in patients treated with BEP. Length of stay was shorter in patients treated with BEP (3.3 v 3.9 days; P < .01). In a modern surgical cohort, the inclusion of bleomycin does not seem to influence pulmonary morbidity, operative difficulty, or nonpulmonary postoperative complications after PC-RPLND in men with IGCCCG good-risk GST.

Retroperitoneal cancer viability after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in good risk germ cell tumors (GCTs).

4551Background: Four cycles of etoposide and cisplatin (EP × 4) or 3 cycles of bleomycin, etoposide, and cisplatin (BEP × 3) is the current standard of care for patients with good-risk testicular c...

Etoposide and cisplatin (EP) for metastatic good-risk germ cell tumors (GCTs): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience in 944 patients (pts).

4550Background: Standard of care for pts with metastatic, good-risk GCTs consists of either 3 cycles of bleomycin, etoposide, and cisplatin (BEPx3) or 4 cycles of EP (EPx4). EPx4 avoids both pulmon...

Survival of good-risk germ cell tumor patients following post-chemotherapy retroperitoneal lymph node dissection: The effect of bleomycin during induction chemotherapy.

4565 Background: Patients presenting with metastatic International Germ Cell Cancer Collaborative Group (IGCCCG) good risk testicular cancer may receive either 4 cycles of etoposide and cisplatin (...

OP3-10 IMPACT OF BLEOMYCIN ON RETROPERITONEAL HISTOLOGY AT POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) IN GOOD RISK GERM CELL TUMORS

You have accessJournal of UrologyOutstanding Posters: Oncology1 Apr 2014OP3-10 IMPACT OF BLEOMYCIN ON RETROPERITONEAL HISTOLOGY AT POST-CHEMOTHERAPY RETROPERITONEAL LYMPH NODE DISSECTION (PC-RPLND) IN GOOD RISK GERM CELL TUMORS K. Clint Cary, Jose Pedrosa, Hristos Kaimakliotis, TImothy Masterson, Lawrence Einhorn, and Richard Foster K. Clint CaryK. Clint Cary More articles by this author , Jose PedrosaJose Pedrosa More articles by this author , Hristos KaimakliotisHristos Kaimakliotis More articles by this author , TImothy MastersonTImothy Masterson More articles by this author , Lawrence EinhornLawrence Einhorn More articles by this author , and Richard FosterRichard Foster More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.2331AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Induction chemotherapy for International Germ Cell Cancer Collaborative Group (IGCCCG) good risk metastatic testicular cancer includes either 3 cycles of bleomycin, etoposide, and cisplatin (BEP) or 4 cycles of etoposide and cisplatin (EP). We sought to examine the differences in active cancer in the retroperitoneum (RP) between patients receiving BEPx3 compared to EPx4. METHODS The Indiana University Testis Cancer database was queried to identify IGCCCG good risk patients who received either BEPx3 or EPx4 induction chemotherapy prior to PC-RPLND. The primary outcome of RP histology was categorized as active cancer (yes/no). The association between use of bleomycin in the induction regimen with active cancer in the RP was tested with logistic regression. A propensity score-adjusted analysis was undertaken to adjust for potential imbalances among men receiving BEP or EP. RESULTS A total of 226 patients met inclusion criteria, some of which were treated at outside institutions. One hundred seventy-nine men (79%) received BEPx3 while 47 (21%) received EPx4. The median age of the BEP group was 27 years (range: 15-50) compared to 30 years (range: 18-71) in the EP group. The BEP group had surgery in earlier years, more often had a right sided primary tumor, and a component of embryonal cell carcinoma in the primary tumor (all p<0.05). The incidence of active cancer in the RP specimen at PC-RPLND was significantly higher in the EPx4 group compared to the BEPx3 group (31.9% vs. 7.8%, p<0.01). This significant difference between the BEP and EP groups remained in the propensity-adjusted analysis (25.5% vs. 8.4%, p=0.01). CONCLUSIONS There was a higher incidence of active cancer in the RP specimen in good risk patients who receive 4 cycles of induction EP chemotherapy compared to men receiving 3 cycles of BEP in this retrospective analysis. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e855 Advertisement Copyright & Permissions© 2014MetricsAuthor Information K. Clint Cary More articles by this author Jose Pedrosa More articles by this author Hristos Kaimakliotis More articles by this author TImothy Masterson More articles by this author Lawrence Einhorn More articles by this author Richard Foster More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Poor-Prognosis Germ Cell Tumors: We Have Not Yet Crossed the Finish Line

Poor-Prognosis Germ Cell Tumors: We Have Not Yet Crossed the Finish Line

High-Dose Chemotherapy for Patients with Poor-Risk Germ-Cell Tumors

Patients with poor-risk germ-cell tumors (as defined by the International Germ Cell Cancer Collaborative Group; J Clin Oncol 1997; 15:594) have a long-term survival rate of about 50%, in contrast to 75% and 90%, respectively, for patients with intermediate- and good-risk germ-cell tumors. Intensification of therapy with multiple active agents and dose intensification of cisplatin, the most active chemotherapy agent for this tumor, have not overcome the inherent drug resistance of poor-risk tumors. However, …

Bleomycin, Etoposide, and Cisplatin for Three Cycles Compared With Etoposide and Cisplatin for Four Cycles in Good-Risk Germ Cell Tumors: Is There a Preferred Regimen?

Bleomycin, Etoposide, and Cisplatin for Three Cycles Compared With Etoposide and Cisplatin for Four Cycles in Good-Risk Germ Cell Tumors: Is There a Preferred Regimen?

Etoposide and Cisplatin Chemotherapy for Metastatic Good-Risk Germ Cell Tumors

To assess response, overall survival, and relapse-free survival of patients with good-risk metastatic germ cell tumor (GCT) by International Germ Cell Consensus Classification Group (IGCCCG) criteria treated with four cycles of etoposide and cisplatin (EP). Two hundred eighty-nine patients with IGCCCG good-risk GCT were treated with four cycles of EP. EP consisted of four cycles of etoposide 100 mg/m2 and cisplatin 20 mg/m2 on days 1 to 5 every 21 days. Two hundred eighty-two of 289 patients (98%) achieved a complete response; 269 (93%) responded to chemotherapy alone and 13 (5%) responded to chemotherapy plus surgical resection of viable disease (GCT other than mature teratoma). Seventeen (6%) experienced relapse, and nine (3%) died as a result of disease at a median follow-up of 7.7 years (range, 0.4 to 21.1 years). Sixty-two of 204 patients (30%) with nonseminoma had findings of teratoma or viable GCT at postchemotherapy surgery. Four cycles of EP is a highly effective therapy for patients with good-risk GCT, with a high cure rate, low relapse rate, and little evidence of late relapse. Postchemotherapy surgery resection of residual disease remains an important aspect of treatment for these patients. Four cycles of EP is acceptable as a standard regimen for the treatment of good-risk metastatic GCT, and serves as an alternative to three cycles of bleomycin and etoposide before cisplatin.

Etoposide and cisplatin (EP) chemotherapy for good risk germ cell tumors (GCT): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

4533 Background: Phase 3 trials at MSKCC showed 4 cycles of EP to be effective and tolerable treatment for good risk advanced GCTs (JCO 1997;15:2553). Additional patients (pts) have been treated and follow-up (f/u) updated to detect late relapses. Methods: 379 pts with good risk GCT received EP from 11/82–12/02 on 4 protocols. MSKCC criteria (Cancer 1991;67:28) were used to assign risk status prospectively until 8/1994. Thereafter, the International Germ Cell Consensus Classification Group (IGCCCG) criteria were used. All pts were retrospectively classified according to IGCCCG criteria. EP consisted of 4 cycles of etoposide 100 mg/m2 and cisplatin 20 mg/m2 days 1–5 every 21 days. Results: 295/379 (78%) had nonseminoma; 84 (22%) had seminoma. Primary site was testis-365 (96%), retroperitoneum-8 (2%), mediastinum-6 (2%). By IGCCCG criteria, 291 (77%) were good risk, 75 (20%) intermediate risk and 13 (3%) poor risk. Of 291 IGCCCG good risk pts, 284 achieved a CR [98%; 273 to chemotherapy (c) and 11 to chemo+...

Etoposide and cisplatin (EP) chemotherapy for good risk germ cell tumors (GCT): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

Etoposide and cisplatin (EP) chemotherapy for good risk germ cell tumors (GCT): The Memorial Sloan-Kettering Cancer Center (MSKCC) experience

Chemotherapy for good-risk germ-cell tumors

Patients with good-risk germ-cell tumors have a high likelihood of cure with an approach that integrates cisplatin-based chemotherapy, surgery, radiation, and observation. This article addresses risk group allocation as well as the controversies regarding the composition, number of cycles, and dosages of chemotherapy regimens used in this population. Recent data from randomized trials demonstrate that carboplatin is inferior to cisplatin and that the dose of etoposide should be 500 mg/m(2) per course. Bleomycin remains controversial in good-risk germ-cell tumors, but the literature suggests that both E(500)P for four cycles or BE(500)P for three cycles may be considered standard.

Cisplatin, etoposide and bleomycin infusion (PEBi regimen) in good-risk patients with germ cell tumors

Patients with good-risk germ cell tumors have an approximately 85-95% chance of cure with standard chemotherapy. However, acute and late toxicity may be severe and negatively influence the quality of life. In an attempt to reduce toxicity, we evaluated a new schedule including bleomycin administered-as a continuous infusion in patients with low and intermediate volume metastatic disease. Patients were treated as follows: cisplatin, 100 mg/m(2) day 4; etoposide, 100 mg/m(2) days 1 through 5; bleomycin, 15 unit bolus on day 1 followed by 30 mg as a continuous infusion for 72 h, with cycles repeated every 21 days. Between 1992 and 1996, 25 patients entered the study and were assessable for response and side effects. Major patient characteristics were: performance status ECOG 0-1; minimal disease, 13 patients, intermediate disease, 12; median age, 33 years (range 15-50). Twenty-one of 25 patients (84%) achieved a complete remission, 2 patients achieved a partial remission, and 2 patients did not respond to the regimen. At a median follow-up of 24 months, 24/25 patients were alive, 23 were without evidence of disease, and I had persistent disease. Grade III/IV side effects included leuko/neutropenia (8 patients), anemia (3 patients), and nausea/vomiting (3 patients). No drug-related deaths were observed, and no evidence of pulmonary toxicity was registered. In conclusion, the PEBi regimen is an effective and well-tolerated regimen in patients with good-risk germ cell tumors and may be considered as a front-line chemotherapy.

Long-term follow-up of patients with good-risk germ cell tumors treated with etoposide and cisplatin.

To assess the durability of response and overall survival for patients with good-risk metastatic germ cell tumors (GCT) treated with four cycles of etoposide and cisplatin (EP). Two hundred fourteen patients treated with EP on two consecutive randomized trials for good-risk metastatic GCT were the subject of this retrospective study. The response to therapy, relapse and survival status, and results of salvage therapy are reported. One hundred ninety-five patients (91%) achieved a complete response (CR). This included 182 patients (85%) who achieved a CR to chemotherapy alone and 13 patients (6%) who achieved a CR to chemotherapy plus surgical resection of viable GCT. Seventeen patients (9%) have relapsed from CR. The median time to relapse was 10 months, and the longest duration from treatment to relapse was 36 months in a patient who received three of four planned courses of therapy. Eight patients who either achieved an incomplete response (IR) or relapsed were rendered continuously disease-free by salvage therapy and are alive. One hundred eighty-three patients (86%) are alive at a median follow-up of 7.6 years. Four cycles of EP constitute effective therapy and can be offered to patients with good-risk GCT. In patients with intermediate- and poor-risk GCT, clinical trials remain a priority to identify more effective treatment.

Cisplatin-etoposide and carboplatin-etoposide induction chemotherapy for good-risk patients with germ cell tumor

In an attempt to reduce the toxicity of chemotherapy in good-risk testicular cancer patients the two drug combinations, cisplatin plus etoposide (EP) and carboplatin plus etoposide (EC), have been compared. Good risk was defined according to the MSKCC and IU criteria. 39 Patients have been treated with EP (cisplatin 20 mg/m2 i.v. and etoposide 100 mg/m2 i.v. on days 1 to 5), and 23 patients received EC (carboplatin 350 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 to 5). Four cycles of chemotherapy were given at 21- and 28-day intervals, respectively, with delays of up to 7 days in instances of leukocyte counts less than 3.0 x 10(9)/l or platelet counts less than 100 x 10(9)/l. In the EP group 34 (87%) of 39 patients achieved CR (26 with chemotherapy alone, 8 with additional surgery). After a median follow-up of 26 (12-58) months 3 (9%) patients relapsed from CR. Currently 38 patients are alive, and 37 (94%) are NED. In the EC group 20 (87%) of 23 patients achieved CR (15 with chemotherapy alone and 5 with additional surgery). After a median follow-up of 45 (26-57) months 6 (30%) patients relapsed from CR. Currently 19 patients are alive and 17 (74%) are NED. There was no difference in survival between the two groups (p = 0.13), but in the EC group the relapse rate was higher (p = 0.052) and the proportion of patients with NED was lower (p = 0.03) in comparison with EP. Toxicity in both groups was mild and similar, but 3 EP-treated patients presented hair loss. The study suggests that carboplatin-etoposide combination therapy is inferior to cisplatin-etoposide in patients with good-risk germ cell tumors.

Serum tumor markers and patient allocation to good-risk and poor-risk clinical trials in patients with germ cell tumors

The allocation of patients with advanced germ cell tumors (GCT) to different treatment programs based on clinical characteristics is standard in the design of clinical trials today. Studies have shown that substantial differences exist between entry criteria and that these differences could influence the outcome of clinical trials. The factors contributing to these differences are not clear due to patient selection biases. Two hundred five unselected and consecutive patients allocated to and treated in good-risk and poor-risk treatment programs at Memorial Sloan-Kettering Cancer Center (MSKCC) were reassigned risk status by the Indiana University (IU) Classification. The results were compared with those of the Southeastern Cancer Study Group (SECSG). The results using both criteria indicated substantial agreement in total end results and the identification of good-risk patients. The results in poor-risk patients differed substantially, with 39 patients (19%) classified as poor-risk by MSKCC criteria and 66 (32%) by Indiana criteria. The major discrepancy occurred in IU Stage 7, in which 26 of 32 patients (81%) achieved a complete response. The major factor contributing to this difference in risk assignment was the use of serum tumor markers. Serum tumor markers must be incorporated into risk assignment criteria for GCT clinical trials to minimize the number of good-risk GCT patients in poor-risk trials.

Two-drug therapy in patients with metastatic germ cell tumors

Eighty-two patients with metastatic germ cell tumors (GCT) treated with two-drug therapy consisting of etoposide and cisplatin were evaluated for late relapse. Good-risk GCT was defined using Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. Etoposide was given at 100 mg/m2 on days 1 to 5 and cisplatin was given at 20 mg/m2 on days 1 to 5; therapy was recycled at 21 days with delays up to 7 days for a leukocyte count of less than 3000/microliters or a platelet count of less than 100,000/microliters. Drug doses were not attenuated for myelosuppression. Seventy-six of 82 evaluable patients achieved a complete response (CR). Seventy-two patients had a CR to chemotherapy alone. Forty-six (56%) patients had excision of residual abnormalities: 11 had teratoma in the resected specimen, 31 had necrotic debris or fibrosis, and 4 had a CR after chemotherapy plus complete excision of residual viable GCT. Six patients had an incomplete response to chemotherapy; one of these patients had unresectable mature teratoma and remains progression-free. The median etoposide dose (+/- standard deviation [SD]) was 500 mg/m2/course (+/- 35 mg/m2) and the median cisplatin dose (+/- SD) was 100 mg/m2/course (+/- 6 mg/m2). Nine patients experienced a relapse at 6 to 17.5 months; two patients with nonseminomatous GCT were salvaged by chemotherapy and one patient with seminoma was salvaged by chemotherapy and radiation therapy. The three patients who were salvaged by additional therapy are disease-free at 59 to 63 months. Seventy-one patients (87%) remain disease-free with a median follow-up time of 63 months (range, 33 to 92 months). No relapses have occurred beyond 17.5 months. Etoposide and cisplatin therapy at these doses and schedule results in durable CR without late relapse.

The effect of a 7-day delay in chemotherapy cycles on complete response and event-free survival in good-risk disseminated germ cell tumor patients

The effect of duration of induction treatment on complete response (CR) and event-free survival (EFS) (time to death or relapse) was evaluated in 162 "good-risk" germ cell tumor (GCT) patients treated from November 1982 to July 1986 in a randomized prospective trial with VAB-6 (cyclophosphamide + vinblastine + bleomycin + dactinomycin + cisplatin; 81 patients) versus etoposide + cisplatin (EP; 81 patients). Patients received three cycles of VAB-6 every 28 days or four cycles of EP every 21 days. Treatment cycle with either regimen was routinely postponed for 7 days for leukocytes less than 3000/mm3 or platelets less than 100,000/mm3 and then administered regardless of blood count. The number of treatment days was calculated for each patient from initial treatment day to final induction date plus 28 days for VAB-6 and plus 21 days for EP. The proportion of CR and the EFS for good-risk GCT patients treated with cisplatin-based chemotherapy were not influenced by a less than or equal to 7-day delay resulting from chemotherapy-induced myelosuppression. Short, planned delays in chemotherapy for good-risk GCT patients (less than or equal to 7 days per cycle) appear to be acceptable since they may prevent serious toxicity in this curable patient population. Delays of longer than 7 days are strongly discouraged except in extraordinary life-threatening circumstances.