Addition of Rituximab to First-Line MCP (Mitoxantrone, Chlorambucil, Prednisolone) Chemotherapy Prolongs Survival in Advanced Follicular Lymphoma - 4 Year Follow-Up Results of a Phase III Trial of the East German Study Group Hematology and Oncology (OSHO#39).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 484-484 ◽  
Author(s):  
Michael Herold ◽  
Antje Haas ◽  
Stephanie Srock ◽  
Sabine Neser ◽  
Kathrin H. Al Ali ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Striking Difference ◽  
P Value ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Increased Risk

Abstract Introduction: Rituximab plus chemotherapy has been proved to be the gold - standard in treating advanced follicular lymphoma. Here we report the 4-year-follow-up data of our phase III trial comparing MCP - chemotherapy vs rituximab + MCP both followed by interferon maintenance in advanced symptomatic follicular lymphoma. Methods: Previously untreated patients with advanced stage (III + IV) symptomatic CD 20-positive indolent NHL and mantle cell lymphoma (n=358) were randomized to receive either MCP-chemotherapy (mitoxantrone 8 mg/m² d1+2, chlorambucil 3x3 mg/m² d 1–5, prednisolone 25 mg/m² d 1–5 x 8 q 4 weeks) or MCP + rituximab (375 mg/m² d −1). Here we report the results of the ITT population of patients with follicular lymphoma (FL) (grade 1+2), who represented the majority of patients and for whom the sample size primarily was calculated, so this is not a subgroup analysis. Study endpoints included overall and complete response rate (RR + CR), progression free survival (PFS), event free survival (EFS), time to next treatment (TTNT), overall survival (OS) and toxicities. Results: with a median follow - up of nearly 4 years (47 months) we are able to provide relatively mature data. Concerning toxicities there was no striking difference, but there was a significantly increased risk to experience a CTC grade III or IV toxicity for leukocytes in the R-MCP arm, however this did not increase the risk of infections. For the FL - ITT population the results are given in the table. Conclusions: Concerning all end points rituximab plus MCP is significantly superior to MCP alone in the treatment of advanced follicular lymphoma. Special attention should be drawn to the fact, that after a median follow-up of 47 months we can demonstrate a clinically and statistically significant survival advantage for the immunochemotherapy. Results R-MCP (n=105) MCP (n=96) p-value Response rate 92,4% 75% .0004 Complete Response 49,5% 25% .0009 PFS median n.r. 29 months < .0001 PSF 4 years 71% 40% EFS median n.r. 26 months < .0001 EFS 4 years 69% 35,5% TTNT median n.r. 29,4 months .0002 OS median n.r. n.r. .0096 OS 4 years 87% 74%

Results of a Prospective Randomised Open Label Phase III Study Comparing Rituximab Plus Mitoxantrone, Chlorambucile, Prednisolone Chemotherapy (R-MCP) Versus MCP Alone in Untreated Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) and Mantle-Cell-Lymphoma (MCL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 584-584 ◽  
Author(s):  
Michael Herold ◽  
Rita Pasold ◽  
Stefanie Srock ◽  
Sabine Neser ◽  
Dietger Niederwieser ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Single Agent ◽  
Complete Response ◽  
Phase Iii ◽  
Published Data ◽  
Event Free Survival ◽  
Serious Adverse Events ◽  
Free Survival ◽  
Phase Ii Studies

Abstract Rituximab proved to be effective in relapsed and refractory indolent NHL as a single agent and generated impressive results in phase II studies in combination with chemotherapy. In a prospective randomized trial we compared the efficacy and toxicity of rituximab (375 mg/m² d 1) plus MCP-chemotherapy ( mitoxantrone 8 mg/m² d 3 + 4, chlorambucile 3 x 3 mg/m² d 3 – 7, prednisolone 25 mg/m² d 3 – 7 ) given every 28 days for a total of 8 cycles versus MCP (d 1 – 5) x 8 cycles alone in advanced indolent NHL and MCL. Efficacy endpoints included overall and complete response rates, event free survival, progression free survival, overall survival and toxicity. For response assessment classical definitions have been used. Between 10/98 and 09/03 we randomized 358 patients (pts) with advanced stage follicular lymphoma (FL) (grade 1 + 2), lymphoplasmacytic lymphoma and MCL to either R-MCP or MCP. The study arms are well balanced for all demographic factors. 201/358 pts (56%) had FL. Both regimens were well tolerated with a low incidence of serious adverse events. The overall response rate (RR) and the complete response rate (CR) for all pts was 85,5% and 42% in the R-MCP arm versus 65,5% and 20% in the MCP arm (p<0,0001). Results were even more impressive in the subgroup of FL pts (n=201) with an overall RR of 92,4% and a CR rate of 49,5% for R-MCP versus 75% and 25% for MCP alone respectively (p<0,0001). In the overall group event free survival (EFS) was significantly prolonged for pts receiving R-MCP vs MCP alone (p<0,001). Median EFS for MCP was 19 months, at this time point EFS for R-MCP was 73%. In FL pts the median EFS for MCP is 19 months too and EFS was 86% for R-MCP at this point. 2-year EFS for all pts was 69% for R-MCP versus 44% for MCP; for FL pts the respective 2-year EFS was 83% for R-MCP and 43% for MCP (p’s<0,0001) (Kaplan Maier estimates). These results compare favourably with the recntly published data of immunochemotherapy for treatment of NHL or MCL. The results from our study confirm the superiority of a combination of rituximab and chemotherapy in the first- line treatment of indolent NHL, primarily follicular lymphoma. The CR rates achieved with the R-MCP regimen are impressive, especially since stricter response criteria were used. In summary we conclude, that the addition of rituximab to MCP chemotherapy improves significantly the outcome of pts with indiolent NHL and MCL.

Capecitabine in operable triple receptor–negative breast cancer: A subgroup analysis of a randomized phase III trial.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 292-292
Author(s):  
C. M. Kelly ◽  
M. C. Green ◽  
K. Broglio ◽  
L. Pusztai ◽  
E. Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Subgroup Analysis ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Phase Iii ◽  
Relapse Free Survival ◽  
Phase Iii Trial ◽  
Free Survival

292 Background: Recent data suggest that patients with operable triple negative breast cancer (TNBC) may derive greater benefit from the addition of capecitabine to anthracycline-taxane regimens. Methods: We examined pathological complete response (pCR), relapse-free survival (RFS) and overall survival (OS) in patients with TNBC randomized to paclitaxel 80mg/m2 weekly (WP) x 12 followed by fluorouracil (500mg/m2), epirubicin (100mg/m2), cyclophosphamide (500mg/m2) every 3 weeks x 4 cycles (FEC) vs. docetaxel (75mg/m2) 3 weekly and capecitabine D1-14 (1500mg/m2 daily; DX) followed by FEC. Patients were stratified by timing of chemotherapy (preoperative vs. adjuvant). Results: 149 patients with TNBC comprising 25% of all patients randomized (N=601). Median age; 49 years (IQR; 41 to 55). The number and proportion of patients by stage were; I (n=32: 21.5%), IIA (n=72: 48.3%), IIB (n=34: 22.8%), IIIA (n=9: 6.0%) and IIIC (n=2; 1.3%). Preoperative therapy was administered to 58 patients (39%) and adjuvant to 91 (61%). There were 17 events (21%) in the DX arm and 10 events (15%) in the WP arm (P=0.36) including 11 distant recurrences in the DX arm and 9 in the WP arm (P=0.99). We observed a pCR in 11 patients (37%) and 10 (36%) in the DX and WP arms respectively (P=0.94). The odds ratio for pCR for patients with TNBC given DX vs. WP was 0.98 (95% CI; 0.33 to 2.80: P=0.94). At 50-months median follow-up the RFS and OS in patients with TNBC randomized to DX or WP was 77% (66 to 86%) and 83% (73 to 92%) (P=0.41) and 78% (67 to 87%) and 87% (77 to 95%) (P=0.16) respectively. RFS and OS for WP vs. DX for non-TNBC was 93% (87 to 95%) and 92% (88 to 96%) (p=0.91) and 96% (92 to 98%) and 97% (94 to 99%) for WP and DX respectively (P=0.39). Conclusions: In this unplanned subgroup analysis there was no difference in pCR, RFS or OS in patients with operable TNBC randomized to WP or DX however, power is limited and should be considered when interpreting these data.

Immunochemotherapy (R-MCP) Is Not Superior to Chemotherapy (MCP) Alone in Advanced Mantle Cell Lymphoma - 42 Months Follow Up Results of the OSHO 39 Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4474-4474
Author(s):  
Michael Herold ◽  
Antje Haas ◽  
Stephanie Srock ◽  
Sabine Neser ◽  
Kathrin H. Al Ali ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Randomised Trial ◽  
Progression Free Survival ◽  
Striking Difference ◽  
P Value ◽  
Free Survival ◽  
Mantle Cell

Abstract Introduction: Rituximab plus chemotherapy has been proved to be the standard in treating advanced follicular lymphoma. However in mantle cell lymphoma (MCL) the results are still controversial. Methods: In a prospective randomised trial (OSHO#39) we compared the efficacy and toxicity of MCP chemotherapy(mitoxantrone 8 mg/m2 d 1+2, chlormabucil 3x3 mg/m2 d 1–5 and prednisolone 25 mg/m2 d q 4 weeks)versus MCP plus rituximab (375 mg/m2 d -1) in advanced indolent lymphoma and mantle cell lymphoma. Here we present the results of the MCL subgroup (n=90) among the 358 randomised patients (FL, MCL, LPL). Study endpoints included overall and complete response rate (RR + CR), progression free survival (PFS), event free survival (EFS), overall survival (OS) and toxicities. Results: with a median follow-up of 43 months for the MCL subgroup we can provide relatively mature data. Concerning toxicities there was no striking difference between the treatment groups. The treatment results for the MCL patients are as follows: Conclusions: Concerning all end-points R-MCP is not superior to MCP chemotherapy alone in advanced mantle cell lymphoma. Immunochemotherapy is obviously not the solution for this poor prognosis lymphoma entity. Results R-MCP n=44 MCP n=46 p-value Response Rate 70,5% 63% .5074 Complete Responses 31,8% 15,2% .0822 PFS median 20,5 months 19 months .2482 PFS 42 months 31% 14% EFS median 19 months 14 months .1369 EFS 42 months 27% 11,5% OS median 56 months 50 months .4862 OS 42 months 60% 61%

scholarly journals Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Noemi Puig ◽  
Miguel T. Hernández ◽  
Laura Rosiñol ◽  
Esther González ◽  
Felipe de Arriba ◽  
...  
Keyword(s):  
Elderly Population ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Unacceptable Toxicity ◽  
Full Trial

AbstractAlthough case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

624 A PHASE III STUDY ON NEOADJUVANT TORIPALIMAB PLUS CHEMOTHERAPY VERSUS NEOADJUVANT CHEMOTHERAPY FOR LOCALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Yan Zheng ◽  
Jiangong Zhang ◽  
Wenqun Xing
Keyword(s):  
Phase Ii ◽  
Checkpoint Inhibitors ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
R0 Resection ◽  
Phase Iii Trial ◽  
Free Survival

Abstract   In recent years, immune checkpoint inhibitors (ICIs) have shown promising results in the treatment of ESCC. More than 20 phase II clinical trials have been launched to explore combinations of ICIs in the neoadjuvant setting for ESCC. Based on our phase II clinical trial, a two-arm phase III trial was launched in our Hospital. Methods A two-arm phase III trial was launched in April 2020 in our Hospital. Patient recruitment will be completed within 18 months. The primary endpoint is event-free survival (EFS). The secondary endpoints include pathologic complete response (pCR), disease-free survival (DFS) rate, overall response rate (ORR), R0 resection rate, major pathologic response (MPR), adverse events (AEs), complication rate and quality of life (QOL). A biobank of pretreatment, resected tumor tissue and paired blood samples will be built for translational research in the future. Results Until Dec. 2021, one hundred and twenty ESCC patients recruited in the trial. The trial is ongoing. Conclusion This RCT directly compares NAC with neoadjuvant toripalimab plus chemotherapy in terms of EFS for locally advanced ESCC. The results may usher in a new era of resectable ESCC treatment.

A Prospective, Randomized, Phase III Study of Melphalan 200 mg/m2 (MEL200) Versus Melphalan 100 mg/m2 (MEL100) in Newly Diagnosed Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 55-55 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Maria Teresa Petrucci ◽  
Antonietta Falcone ◽  
Anna Marina Liberati ◽  
...  
Keyword(s):  
Stem Cell ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Psychiatric Disease ◽  
High Dose ◽  
Free Survival ◽  
Grade 3

Abstract Several trials have shown the superior impact of high-dose melphalan (usually 200 mg/m2, MEL200) versus standard therapy in myeloma patients. Intermediate-dose melphalan (100 mg/m2, MEL100) was also superior to the standard dose, but MEL100 has not been clinically compared with MEL200 in a randomized study. In a case-matched study, response rate and event-free survival of MEL200 were superior to MEL100, but overall survival (OS) was similar. In this prospective, randomized, phase III trial, we compared the efficacy and toxicity of MEL200 and MEL100. Between January 2002 and July 2006, 299 patients were enrolled. Inclusion criteria were previously untreated myeloma, aged < 65 and Durie and Salmon stage II or III. Exclusion criteria were abnormal cardiac function, respiratory disease, abnormal liver function, abnormal renal function, HBV, HCV, or HIV positivity, concomitant cancer or psychiatric disease. The institutional review board approved the protocol and written informed consent was obtained from all patients. All patients received: 2 dexamethasone-doxorubicin-vincristine debulking courses (doxorubicin 50 mg/m2 day 1, vincristine 1 mg day 1, dexamethasone 40 mg days 1, 2, 3, 4, each course repeated every 28 days), 2 cycles of cyclophosphamide (4 g/m2, day 1) plus G-CSF followed by stem cell harvest. The MEL200 group was conditioned with 2 cycles of melphalan 200 mg/m2 followed by stem cell reinfusion; the MEL100 group was conditioned with 2 courses of melphalan 100 mg/m2 followed by stem cell reinfusion. At the present, 246 patients, median age 57 (range 32–65), completed the assigned therapy and were evaluated for response, progression-free survival (PFS) and OS. One-hundred and twenty-four patients were randomized to MEL200 and 122 to MEL100. Patient characteristics were similar in both groups. Abnormal cytogenetics (13q deletion, t(4;14), t(11;14), p53) were 75% in MEL200 patients and 56% in MEL100 patients (p=0.05). Forty-six patients did not complete tandem MEL200; 36 patients did not complete tandem MEL100. The near complete response rate of MEL200 was superior to MEL100 (32% versus 18%, p=0.011), but partial response was 80% versus 71%, respectively (p=0.079). The median follow-up for censored patients was 26.5 months. The 3 years PFS was 51% in the MEL200 arm and 33% in the MEL100 arm (HR=0.81, 95% CI 0.55–1.21, p=0.31). The 3 years OS was 86% in the MEL200 group and 71% in the MEL100 group (HR=0.82, 95 CI 0.45–1.48, p=0.51). Duration of grade 4 neutropenia and thrombocytopenia was comparable in two arms, but MEL200 patients required more platelet transfusions (p=0.03). Grade 3–4 non-hematological adverse events were reported in 49% of the MEL200 patients and in 38% of the MEL100 patients (P=0.07). The most frequent grade 3–4 adverse events were infections (54% of MEL200 patients versus 45% of MEL100 patients, p=0.25), mucositis (31% of MEL200 patients versus 7% of MEL100 patients, p=0.002) and gastrointestinal toxicities (20% of MEL200 patients versus 14% of MEL100 patients, p=0.3). In conclusion, MEL200 resulted in a significantly higher near complete response rate but this did not translate in a superior PFS and OS.

Rituximab Maintenance Treatment for a Maximum of 5 Years In Follicular Lymphoma: Safety Analysis of the Randomized Phase III Trial SAKK 35/03

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1802-1802 ◽  
Author(s):  
Christian J. Taverna ◽  
Simona Bassi ◽  
Felicitas Hitz ◽  
Walter Mingrone ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Safety Analysis ◽  
Phase Iii ◽  
Advisory Committees ◽  
Phase Iii Trial ◽  
Rituximab Maintenance ◽  
Grade 3 ◽  
Unacceptable Toxicity

Abstract Abstract 1802 Background: Rituximab maintenance has been shown to be effective in patients with follicular lymphoma. The optimal duration of maintenance remains unknown. Methods: We prospectively registered 270 patients with untreated, chemotherapy resistant or relapsed follicular lymphoma. All patients received rituximab induction consisting of 4 weekly doses (375 mg/m2). Responding patients (PR and CR) were randomized to a short maintenance consisting of four doses of rituximab (375 mg/m2) every two months (arm A) or prolonged maintenance consisting of rituximab every two months for a maximum of five years or until disease progression or unacceptable toxicity (arm B). Primary endpoint is event-free survival. Here we present the safety analysis results after a median long-term maintenance period of 3.3 years. Results: From October 2004 to November 2007 165 patients were randomized, 82 in arm A and 83 in arm B. The median follow-up time is 3.2 years for arms A and B combined. While receiving maintenance therapy a total of 899 hematological and non-hematological adverse events were observed, 28 of grade 3 and 6 of grade 4. After randomization five patients experienced subsequent cancers. Seven grade 3 and 4 infections were reported. Two grade 3 infections occurred after 2 years of maintenance. Grade 3 and 4 neutropenia occurred in 6 (3.6 %) patients, decreased levels of IgG were observed in 24 (14.6 %) patients. In arm B, maintenance was stopped due to unacceptable toxicity in 2 patients after 16 and 42 months respectively and due to subsequent breast cancer in 1 patient after 20 months. One patient died 4 months after randomization because of ileus and consecutive peritonitis, considered to be unrelated to therapy. Sixty-three patients are on maintenance for two or more years of which 48 patients are on for three or more years. Two patients have completed the 5 years of maintenance. Conclusions: Rituximab maintenance beyond two years is feasible without evidence for increased toxicity. However, close follow up of patients under prolonged rituximab maintenance is still necessary. The trial has been closed for accrual but there are still patients on treatment. Disclosures: Taverna: Roche: Membership on an entity's Board of Directors or advisory committees. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Late toxicities and recurrences in patients with clinical stage I nonseminomatous germ cell tumor after one cycle of adjuvant BEP versus primary retroperitoneal lymph node dissection: A 13-years follow-up analysis of a phase III trial cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5512-5512
Author(s):  
Andreas Hiester ◽  
Anna Fingerhut ◽  
Guenter Niegisch ◽  
Roswitha Siener ◽  
Susanne Krege ◽  
...  
Keyword(s):  
Germ Cell ◽  
Clinical Stage ◽  
Cell Tumor ◽  
Phase Iii ◽  
Testis Cancer ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Nonseminomatous Germ Cell Tumor

5512 Background: One cycle of adjuvant BEP has shown superiority in recurrence free survival over RPLND in patients (pts) with clinical stage (CS) I nonseminomatous germ cell tumor of the testis (NSGCT) (JCO 2008). We report recurrences and late toxicities of this randomized trial after 13 yrs of follow-up (FU). Methods: Questionnaires of 382 unselected pts with CS I NSGCT treated within a phase III trial comparing recurrence rate after 1 cycle of adjuvant BEP (arm A) vs. RPLND (arm B) were evaluated regarding recurrences and late toxicity. Overall (OS) and progression free survival (PFS) was calculated by Kaplan-Meier and arms were compared using logrank test. Categorial data were analyzed by chi-square test (PRISM v8). Results: In each arm 191 pts were analyzed as intention-to-treat with a median FU of 13.75 yrs (0-22.9 yrs); 3/191 pts (1.6 %) in arm A and 16/191 pts (8.4 %) in arm B had a recurrence. 20-yrs PFS in arm A / B was 97 % (CI 96-99 %) / 92 % (CI 90-95 %), ( p = .0049). 20-yrs OS in arm A / B was 90 % (CI 86-94 %) / 88 % (CI 86-94 %), ( p = .83). 23/382 (6 %) pts have died, 22/23 not related to testis cancer, 1/23 died of a recurrence in arm B. 8/191 pts (4.2 %) in arm A and 4/191 pts (2.1 %) in arm B showed metachronous secondary testis cancer ( p = .26). 5/191 pts (2.6 %) in arm A and 4/191 pts (2.1 %) in arm B developed other malignancies. 170/382 questionnaires were evaluable (arm A: 95; arm B: 75). 45 pts were lost to FU. There were no significant differences comparing both treatment arms regarding potentially treatment-related late toxicities. However, excluding pre-existing complaints, ototoxicity (9/95 (9 %) vs. 4/75 (5 %) pts, p = .31) was reported more frequently in arm A. Excluding pre-existing neurological conditions, peripheral neuropathy of all grades was more frequently reported in arm A (15/95 pts; 16 % vs. 9/75 pts; 12 % pts; p = .48). Retrograde ejaculation occurred more frequently after RPLND (9/95 pts; 9% vs. 18/75 pts; 24 %, p = .01). Conclusions: After more than 13 yrs of FU, recurrences in non-risk factor selected pts with CS I NSGCT remain to be significantly more frequent with RPLND. No excess mortality due to secondary malignancies was observed. Late toxicities did not differ between 1 cycle of BEP and RPLND. Only retrograde ejaculation was observed significantly more frequent after RPLND. With long-term observation, 1 cycle of BEP has not only a high efficacy to prevent recurrence but also seems to be tolerated without clinically relevant long-term toxicity.

Bortezomib Added to R-CVP Is Safe and Effective for Previously Untreated Advanced-Stage Follicular Lymphoma: A Phase II Study by the National Cancer Institute of Canada Clinical Trials Group

2011 ◽  
Vol 29 (25) ◽  
pp. 3396-3401 ◽  
Author(s):  
Laurie H. Sehn ◽  
David MacDonald ◽  
Sheldon Rubin ◽  
Guy Cantin ◽  
Morel Rubinger ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Complete Response Rate ◽  
Standard Dose ◽  
Complete Response ◽  
Phase Iii ◽  
High Risk Population ◽  
Advanced Stage ◽  
Grade 3

Purpose Bortezomib has demonstrated promising activity in patients with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of bortezomib added to rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) in previously untreated advanced-stage FL. Patients and Methods This is a phase II multicenter trial adding bortezomib (1.3 mg/m2 days 1 and 8) to standard-dose R-CVP (BR-CVP) for up to eight cycles in patients with newly diagnosed stage III/IV FL requiring therapy. Two co-primary end points, complete response rate (complete response [CR]/CR unconfirmed [CRu]) and incidence of grade 3 or 4 neurotoxicity, were assessed. Results Between December 2006 and March 2009, 94 patients were treated with BR-CVP. Median patient age was 57 years (range, 29 to 84 years), and the majority had a high (47%) or intermediate (43%) Follicular Lymphoma International Prognostic Index score. BR-CVP was extremely well tolerated, with 90% of patients completing the intended eight cycles. No patients developed grade 4 neurotoxicity, and only five of 94 patients (5%; 95% CI, 0.8% to 9.9%) developed grade 3 neurotoxicity, which was largely reversible. On the basis of an intention-to-treat analysis, 46 of 94 patients (49%; 95% CI, 38.8% to 59.0%) achieved a CR/CRu, and 32 of 94 patients (34%) achieved a partial response, for an overall response rate of 83% (95% CI, 75.4% to 90.6%). Conclusion The addition of bortezomib to standard-dose R-CVP for advanced-stage FL is feasible and well tolerated with minimal additional toxicity. The complete response rate in this high-risk population compares favorably to historical results of patients receiving R-CVP. Given these results, a phase III trial comparing BR-CVP with R-CVP is planned.

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