Combination of Bortezomib, Melphalan, Prednisone and Thalidomide (VMPT) for Relapsed Multiple Myeloma: Results of a Phase I/II Clinical Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 407-407 ◽  
Author(s):  
Antonio Palumbo ◽  
Maria Teresa Ambrosini ◽  
Giulia Benevolo ◽  
Patrizia Pregno ◽  
Norbert Pescosta ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Response Rate ◽  
Oral Prednisone ◽  
Progression Free Survival ◽  
Complete Response ◽  
Second Line ◽  
Open Label ◽  
Free Survival ◽  
Line Of Therapy

Abstract BACKGROUND: In newly diagnosed patients, the addition of thalidomide or bortezomib (Velcade™) to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter, open-label, non randomized, phase I/II trial, the safety/efficacy profile of the 4 drug combination, bortezomib (Velcade™), melphalan, prednisone, and thalidomide (VMPT) was evaluated in patients with relapsed/refractory myeloma. METHODS: Bortezomib was administered by IV bolus on days 1, 4, 15, 22 at three dose levels: in the first cohort (10 patients) at 1.0 mg/m2; in the second cohort (10 patients) at 1.3 mg/m2and in the third cohort (10 patients) at 1.6 mg/m2. Oral melphalan was administered at 6 mg/m2 on days 1–5, oral prednisone at 60 mg/m2 on days 1–5. Thalidomide was delivered at 50 mg on days 1–35. Each course was repeated every 35 days for a total of 6 courses. RESULTS: Thirty patients, median age 66 years (range 38–79), with relapsed or refractory myeloma were enrolled. Fourteen patients received VMPT as second line of therapy, 16 as third line. Twenty patients received prior autologous transplant, 10 conventional chemotherapy and 9 thalidomide-based regimens. After a median of 6 courses, 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good partial response (VGPR). Among patients who received VMPT as second line treatment, the PR rate was 79%, and the immunofixation negative complete response rate 36%. The 1-year progression-free survival was 61%, and the 1-year survival from study entry was 84%. Grade 3 non-hematological adverse events included: infections (5 patients), fatigue (1), vasculitis (1) and peripheral neuropathy (2); no grade 4 toxicities were recorded. CONCLUSIONS: Initial results showed that VMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. The incidence of neurotoxicities was unexpectedly low.

Weekly Topotecan for Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma: Tolerability and Efficacy Study—The Israeli Experience

2013 ◽  
Vol 23 (3) ◽  
pp. 475-480 ◽  
Author(s):  
Tamar Safra ◽  
Tara Berman ◽  
Adelya Yachnin ◽  
Ilan Bruchim ◽  
Mihai Meirovitz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Partial Response ◽  
Clinical Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Tubal Cancer ◽  
Grade 3

ObjectivesThe purpose of this study was to assess the clinical activity and toxicity of weekly topotecan in a large cohort of epithelial ovarian (EOC), primary peritoneal (PPC), and tubal cancer patients.MethodsRecords of patients with recurrent EOC, PPC, and tubal cancer who were treated with weekly topotecan (4.0 mg/m2 on days 1, 8, and 15 on a 28-day cycle) after failure of more than 1 prior regimen were retrospectively reviewed in 8 centers in Israel.ResultsTwo hundred four patients were evaluated for efficacy and toxicity. Median age was 62 years (range, 27–89 years); 121 (59.3%) were platinum sensitive. Patients were exposed to a median of 2 previous lines (range, 1–9), and 48.5% received only 1 prior chemotherapy regimen. Median follow-up was 15.5 months (range, 2.5–112 months). Overall response rate was 26.5%, of which 11 patients (5.4%) had complete response, and 43 patients (21.1%) had partial response. Clinical benefit rate (complete response + partial response + stable disease) was 65.7%. Median progression-free survival was 4.0 months (95% confidence interval [CI], 3.5–4.5 months). There was no significant difference between platinum-sensitive and platinum-resistant patients regarding response rate or progression-free survival. Median overall survival from disease diagnosis was 45.0 months (95% CI, 40.04–49.6 months) and 16.0 months (95% CI, 12.3–19.7 months) from initiation of topotecan therapy. Overall survival was significantly different between patients with platinum-sensitive and platinum-resistant disease (19.9 vs 10.8 months, respectively, P = 0.003; 95% CI, 8.1–16.3 months). Multivariate analysis showed that only platinum sensitivity and topotecan line were associated with overall survival. Weekly topotecan was well tolerated—with only 16.7% of patients experiencing grade 3 to 4 hematologic toxicities. There were no other grade 4 toxicities, and only 6.9% grade 3 toxicities.ConclusionsIn this large cohort of recurrent EOC, PPC, and tubal cancer, weekly topotecan was well tolerated with good clinical benefit rate, comparable to previous studies.

Treatment sequencing patterns for relapsed refractory multiple myeloma (RRMM) in the era of new therapies in a single center institution.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19513-e19513
Author(s):  
Alexandre Tungesvik ◽  
Praneeth Reddy Sudalagunta ◽  
Jessica Huang ◽  
Elizabeth Dimaggio ◽  
Gabe De Avila ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Therapy ◽  
Cancer Center ◽  
Free Survival ◽  
New Therapies ◽  
First Response ◽  
Line Of Therapy

e19513 Background: Although there is much to be optimistic about in the multiple myeloma community as the approval of new therapies and regimen-combinations for relapsed refractory disease continues to grow, determining the best option for a patient can be complicated. Both carfilzomib- (C) and daratumumab- (D) based regimens have demonstrated superior efficacy in this setting, but there is a paucity of data supporting which should be selected first, and if regimen sequence influences outcomes. The aim of this study is to describe sequencing patterns in the era of these newer agents and to determine if there is a difference in outcomes for patients with RRMM who received one of the following treatment sequences: C-regimen with a D-regimen given immediately prior (DC); C-regimen without any prior D (C only); D-regimen with a C-regimen given immediately prior (CD); or D-regimen without any prior C (D only). Methods: This is a retrospective analysis of patients with RRMM consecutively treated at Moffitt Cancer Center between 1/1/2015 and 6/25/18. Response to therapy was assessed using the International Myeloma Working Group (IMWG) criteria. Progression-free survival (PFS) was measured in days from the start of therapy to progression. Time to response (TTR) was measured in days from the start of therapy to first response. Results: 132 patients with RRMM who received 1-3 prior lines of therapy with at least one line of therapy containing either C or D were identified. Overall, the majority of patients were treated with C only (n = 101), 10 received DC, 31 received D only, and 35 received CD. In patients that received C only, partial response (PR) was achieved in 38%, very good partial response (VGPR) was 20%, and stringent complete response (sCR) was 2%. In patients that received DC, PR was 20% and VGPR was 10%; no patient achieved a sCR. Of the patients that received D only, PR was 29%, VGPR was 10%, and sCR was 3%. In patients that received CD, PR was 31% and VGPR was 26%; no patient achieved sCR. Median PFS in patients who received C only, DC, D only, and CD was 117 days, 126 days, 104 days, and 190 days, respectively. TTR in patients who received C only, DC, D only, and CD was 82 days, 39 days, 98 days, and 88 days, respectively. Conclusions: The data suggests that RRMM patients who receive either CD or DC appear to have a PFS advantage over those patients who did not. Notably, an early TTR was found in patients that received DC. Further analysis is ongoing.

Combination of Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) in Relapsed/Refractory Multiple Myeloma: Results of a Multicenter Phase II Clinical Trial

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 868-868 ◽  
Author(s):  
Antonio Palumbo ◽  
Patrizia Falco ◽  
Grazia Sanpaolo ◽  
Antonietta Falcone ◽  
Vincenzo Ferderico ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Drug Combination ◽  
Response Rate ◽  
Oral Prednisone ◽  
Cell Transplant ◽  
Second Line ◽  
Open Label ◽  
Grade 3

Abstract Background: In newly diagnosed multiple myeloma (MM) patients the addition of lenalidomide or thalidomide or bortezomib to the standard oral melphalan and prednisone (MP) combination significantly increased response rate and event-free survival. In advanced MM, the 4 drug combination VMPT further improves response rate. In this multicenter open label phase I/II trial the safety/efficacy profile of the 4 drug combination, lenalidomide, melphalan, prednisone and thalidomide (RMPT) was evaluated in patients with relapsed/refractory myeloma. Methods: Oral lenalidomide was administered at 10 mg/day on days 1–21, oral melphalan at 0.18 mg/kg on days 1–4, oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1–28. Each course was repeated every 28 days for a total of 6 courses. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Maintenance therapy included lenalidomide alone at 10 mg/day on days 1–21. Results: Forthy-four patients, median age 69 years (range 47–80), with relapsed or refractory MM were enrolled. Twenty-six patients received RMPT as second line of therapy, 18 as third line. Twenty patients received prior autologous transplant, 10 thalidomide-based regimen, 9 bortezomib-based regimen and 3 allogeneic stem cell transplant. After a median of 2 courses, 75.8% of patients achieved at least a partial response (PR), including 30% very good partial response (VGPR). Among patients who received RMPT as second line therapy the PR rate was 81.8%, including VGPR 36.4%.Among patients who received thalidomide 100 mg, the PR rate was 93.3% (including VGPR 46.7%) compared to 64.7% of thalidomide 50 mg. The 1-year-progressionfree survival was 48.6% and the 1-year survival from study entry was 90%. Grade 3–4 hematologic adverse events included: neutropenia (66.6%), thrombocytopenia (36.3%) and anemia (30.2%). Grade 3–4 non hematologic adverse events included: infections (21.2%), neurological toxicity (6%) and fatigue (9%). No thromboembolic events were reported. Conclusion: Initial results showed that RMPT is an effective salvage therapy with a high proportion of responses. Toxicities were manageable. No thromboembolic complications were reported.

scholarly journals Sequential Intravenous to Oral Proteasome Inhibitor Based Regimens for the Treatment of Newly Diagnosed Multiple Myeloma Patients: A Real-World Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Aijun Liu ◽  
Rong Fu ◽  
Zunmin Zhu ◽  
Li Bao ◽  
Huizheng Bao ◽  
...  
Keyword(s):  
Partial Response ◽  
Real World ◽  
Proteasome Inhibitor ◽  
Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Continuous Therapy ◽  
Before And After

Objective To assess in-class transition (iCT) from intravenous bortezomib-based induction to all-oral ixazomib-based treatment improving proteasome inhibitor-based continuous therapy with efficiency, safety and convenience in clinical practice. Methods In this real-world retrospective study from Chinese seven hospitals during Oct, 2017-Jul, 2020, we analysed newly diagnosed multiple myeloma (NDMM) patients without transplantation, who achieved at least partial response of bortezomib-based introduction, and then received ixazomib-based regimen for 2 years or until progression/intolerant toxicity. Primary endpoint: progression-free survival (PFS). Key endpoints included response rate, therapy duration and adverse event (AE). Results 96 patients were enrolled in this study (median age 61 years; 25% ≥ 65 years; 7% ≥ 75 years; 61% male; ISS stage I/II/III 10%/35%/55%; IgG/IgA/IgD/IgE/light chain /double clonal /non-secretory 50%/18%/2%/1%/26%/1%/2%). R-ISS stage was estimated in 85 patients (stage I/II/III 6%/78%/16%). 35% high risk(HR) (27/78) and 65% standard risk (SR)(51/78) were tested by metaphase fluorescence in situ hybridization (M-FISH) according to Mayo clinic risk stratification. 96 patients received median 5 cycles (2-12) of bortezomib-based regimen including VD1/VRD1/VTD1/VCD1/PAD1/PD2D1, and median 6 cycles (1-17) of iCT regimen including ID1/IRD1/ITD1/ICD1 (30/96,43/96,10/96,13/96), three-drug ixazomib-based regimens account for the majority (66/96). Median duration of total PI therapy was 11.3 months and of ixazomib-based regimen was 5.3 months. With 13 months median follow-up, 18-month progression free survival (PFS) rate was 87% (95% confidence interval,78-95) from the start of bortezomib-based induction and 82% (95% confidence interval,70-94) from the start of ixazomib-based treatment(Figure 1A), 79% patients remain on therapy at data cutoff. After bortezomib-based induction, overall response(ORR) rate was 100% (strict complete response [sCR], 10/96, 10%; complete response [CR], 31/96, 32%; very good partial response [VGPR], 24/96, 26%; partial response [PR], 31/96, 32%) and 88% (sCR 22/96, 23%; CR, 28/96, 29%; VGPR, 16/96, 17%; PR, 18/96, 19%) at data cutoff. There were 3 PR improved to VGPR, 4 VGPR improved to CR, 1 PR, 4 VGPR and 5 CR improved to sCR (Figure 1B). ORR of HR patients were 100% and 85%(23/27), 1 PR improved to VGPR, 1PR improved to CR, 4CR improved to sCR; ORR of SR patients were 100% and 85% (45/51), 2PR improved to VGPR, 5VGPR improved to CR, 4VGPR and 3CR improved to sCR, before and after ixazomib-based regimen, respectively. Among 66 patients who transited to IRD1/ITD1/ICD1 regimen, medium duration of total PI therapy was 11.0 months and of ixazomib-based regimen was 5.4 months, 77% patients remain on therapy. ORR rate was 100% (sCR, 7/66, 11%; CR, 16/66, 24 %; VGPR, 16/66, 24%; PR, 27/66, 41%) and 91% (sCR 15/66, 23%; CR, 18/66, 27%; VGPR, 9/66, 14%; PR, 18/66, 27%) at data cutoff, 3 PR improved to VGPR, 4PR and 6 VGPR improved to CR, 4 VGPR and 3 CR improved to sCR. ORR of HR (23/52) patients were 100% and 96%, ORR of SR patients (29/52)were 100% and 86% before and after ixazomib-based regimen, respectively. The ixazomib-safety profile was consistent with previous clinical trial data. In our study, 59% (57/96) of patients had any grade adverse events AE. In which, the most frequent grade <=2 AEs were peripheral neuropathy(PN) (31%, 31/96, PN of 23 patients began after bortezomib-based induction), nausea and vomiting (33%), diarrhea (5%), constipation (4%), incomplete intestinal obstruction (3%), fatigue (2%), edema (1%), abdominal distension (1%) , anorexia (1%), rash(1%) , weakness of lower limbs (1%). The most frequent grade 3/4 AEs were agranulocytosis (2%) , rash (2%), PN (2%, occurred after bortezomib-based induction). Treatment discontinued of ixazomib-based regimen are PN (6/96), incomplete intestinal obstruction (1/96), agranulocytosis (1/96), rash (2/96). Conclusion In real-world China MM population, NDMM patients are sensitive to PI-based continuous therapy with satisfied response rate; iCT can permit prolonged PI-based therapy with promising efficacy and tolerated adverse events. Note: VD1, VRD1, VTD1, VCD1, PAD1, PD2D1, IRD1, ITD1, ICD1 : I: ixazomib, R: lenalidomide, T: thalidomide, C: cyclophosphamide, V: bortezomib, D1: dexamethasone P: bortezomib, A: adriamycin D2: liposome doxorubicin Disclosures No relevant conflicts of interest to declare.

A Prospective Randomized Phase I/II Study of Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) for Relapsed/Refractory Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2864-2864 ◽  
Author(s):  
Federica Cavallo ◽  
Alessandra Larocca ◽  
Maria Teresa Petrucci ◽  
Vincenzo Federico ◽  
Antonietta Pia Falcone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Phase I ◽  
Response Rate ◽  
Oral Prednisone ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3

Abstract Abstract 2864 Poster Board II-840 Background. New drug associations may improve patients outcome in relapsed/refractory multiple myeloma (MM). In newly diagnosed MM patients the addition of lenalidomide or thalidomide or bortezomib, to the standard oral melphalan and prednisone combination significantly increased response rate and event-free survival, showing synergistic effects. Aims. This is a multicenter, randomized, open label phase I/II trial designed to evaluate the safety/efficacy profile of the salvage treatment, Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) in patients with relapsed/refractory myeloma. Methods. Oral lenalidomide was administered at 10 mg/day on days 1-21, in combination with oral melphalan at 0.18 mg/kg on days 1–4 and oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1-28. Each course was repeated every 28 days for a total of 6 courses. Maintenance therapy included Lenalidomide alone at 10 mg/day on days 1-21. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Results. Forthy-four patients with relapsed/refractory MM were enrolled in the study between May 2007 and March 2008, including 22 patients in arm A and 22 patients in arm B. After a median of 5 cycles 75% of patients achieved at least a partial response (PR), including 20% very good partial response (VGPR) and 14% near or complete response (nCR or CR). Among patients who received thalidomide 100 mg, the PR rate was 82% (including 23% VGPR and 23% CR/nCR). Higher response rate was observed among patients who received RMPT in first relapse. The 1-year-progression-free survival was 51,5% and the 1-year survival from study entry was 72%. Hematologic toxicity was the most frequent adverse event. Grade 3-4 hematologic adverse events included: neutropenia (68%), thrombocytopenia (36%) and anemia (32%). Grade 3-4 non hematologic adverse events included: infections (22,7%), neurological toxicity (4,5%) and fatigue (6,8%). No grade 3-4 thromboembolic events were reported. Conclusion. This is the first trial exploring the association of two immunomodulatory drugs, Thalidomide and Lenalidomide. RMPT is an active regimen in patients with relapsed/refractory MM. Toxicities were manageable and the incidence of neutrotoxcities was low. Updated results will be presented at the time of the meeting. Disclosures: Cavallo: CELGENE: Honoraria. Petrucci:CELGENE: Honoraria. Canepa:CELGENE: Honoraria. Boccadoro:CELGENE: CONSULTANCY, ADVISORY COMMITTEES, Research Funding. Palumbo:CELGENE: Honoraria.

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.

scholarly journals Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kuo-Chen Wei ◽  
Peng-Wei Hsu ◽  
Hong-Chieh Tsai ◽  
Ya-Jui Lin ◽  
Ko-Ting Chen ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Progression Free Survival ◽  
Multicenter Trial ◽  
Newly Diagnosed ◽  
Open Label ◽  
Free Survival ◽  
Asian Patients ◽  
Newly Diagnosed Glioblastoma ◽  
Secondary Endpoints

AbstractAsunercept (company code APG101 [Apogenix AG]; company code CAN008 [CANbridge Pharmaceuticals]) is a novel glycosylated fusion protein that has shown promising effectiveness in glioblastoma. This Phase I study was initiated to evaluate the tolerability and safety of asunercept in combination with standard radiotherapy and temozolomide (RT/TMZ) in Asian patients with newly diagnosed glioblastoma. This was the Phase I portion of a Phase I/II open label, multicenter trial of asunercept plus standard RT/TMZ. Adults with newly-diagnosed glioblastoma received surgical resection followed by standard RT/TMZ plus asunercept 200 mg/week (Cohort 1) or 400 mg/week (Cohort 2) by 30-min IV infusion. The primary endpoint was the safety and tolerability of asunercept during concurrent asunercept and RT/TMZ; dose-limiting toxicities were observed for each dose. Secondary endpoints included pharmacokinetics (PK) and 6-month progression-free survival (PFS6). All patients (Cohort 1, n = 3; Cohort 2, n = 7) completed ≥ 7 weeks of asunercept treatment. No DLTs were experienced. Only one possibly treatment-related treatment emergent adverse event (TEAE), Grade 1 gingival swelling, was observed. No Grade > 3 TEAEs were reported and no TEAE led to treatment discontinuation. Systemic asunercept exposure increased proportionally with dose and showed low inter-patient variability. The PFS6 rate was 33.3% and 57.1% for patients in Cohort 1 and 2, respectively. Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016.

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

2020 ◽  
Author(s):  
Ke Cheng ◽  
Yu-Wen Zhou ◽  
Ye Chen ◽  
Zhi-Ping Li ◽  
Meng Qiu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Overall Response Rate ◽  
Progression Free Survival ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Free Survival ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

Abstract Background Irinotecan-based doublet chemotherapy strategy was standard second-line backbone treatment for patients with oxaliplatin‑refractory metastatic colorectal cancer(mCRC). The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients.Methods The study was a single-center, non-randomized, open-label phase II trial. Patients with mCRC after failure with first-line treatment of oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival, and the secondary endpoints included overall response rate, disease control rate, overall survival and treatment related adverse events. Results Between December 2012 and October 2016, 35 patients were enrolled. 33 and 35 patients were assessed for response and safety, respectively. The overall response rate (ORR) was 8.6 %, and the disease control rate (DCR) was 71.4%. The median progression-free survival (PFS) was 4.5 months (95% CI 3.8–5.2). The median overall survival was 12.0 months (95% CI 8.5–15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 hematological adverse events were leukopenia (8.6%), neutropenia (5.7%). The most common grade 3/4 nonhematological adverse events were anorexia (14.3%), vomiting (14.3%), nausea (11.4%) and fatigue (8.6%). Two patients discontinued the protocol treatment because of treatment-related gastrointestinal adverse events. No one died from treatment-related events. The incidence and severity of toxicity was irrelevant to UGT1A1 status.Conclusions The combination of irinotecan with raltitrexed is an active, convenient and acceptable toxic regimen for second-line treatment for mCRC patients, which needs further study as a chemotherapy backbone to be combined with targeted agents in mCRC.Trial registration No. ChiCTR-ONC-12002767. The study was registered with the Chinese Clinical Trial Registry at 29 Octorber 2012, http://www.chictr.org.cn/index.aspx.

ABVD Versus Modified Stanford V Versus MOPPEBVCAD With Optional and Limited Radiotherapy in Intermediate- and Advanced-Stage Hodgkin's Lymphoma: Final Results of a Multicenter Randomized Trial by the Intergruppo Italiano Linfomi

2005 ◽  
Vol 23 (36) ◽  
pp. 9198-9207 ◽  
Author(s):  
Paolo G. Gobbi ◽  
Alessandro Levis ◽  
Teodoro Chisesi ◽  
Chiara Broglia ◽  
Umberto Vitolo ◽  
...  
Keyword(s):  
Adjuvant Radiotherapy ◽  
Hodgkin’S Lymphoma ◽  
Response Rate ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Drug Doses ◽  
Advanced Hodgkin’S Lymphoma

Purpose In this multicenter, prospective, randomized clinical trial on advanced Hodgkin's lymphoma (HL), the efficacy and toxicity of two chemotherapy regimens, doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) and mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine (MOPPEBVCAD), were compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as standard therapy to select which regimen would best support a reduced radiotherapy program, which was limited to ≤ two sites of either previous bulky or partially remitting disease (a modification of the original Stanford program). Patients and Methods Three hundred fifty-five patients with stage IIB, III, or IV HL were randomly assigned. Three hundred thirty-four patients were assessable for the study and received six cycles of ABVD (n = 122), three cycles of Stanford V (n = 107), or six cycles of MOPPEBVCAD (n = 106); radiotherapy was administered to 76, 71, and 50 patients in these three arms, respectively. Results The complete response rates for ABVD, Stanford V, and MOPPEBVCAD were 89%, 76% and 94%, respectively; 5-year failure-free survival (FFS) and progression-free survival rates were 78%, 54%, 81% and 85%, 73%, and 94%, respectively (P < .01 for comparison of Stanford V with the other two regimens). Corresponding 5-year overall survival rates were 90%, 82%, and 89% for ABVD, Stanford V, and MOPPEBVCAD, respectively. Stanford V was more myelotoxic than ABVD but less myelotoxic than MOPPEBVCAD, which had larger reductions in the prescribed drug doses. Conclusion When associated with conditioned and limited (not adjuvant) radiotherapy, ABVD and MOPPEBVCAD were superior to Stanford V chemotherapy in terms of response rate and FFS and progression-free survival. Patients were irradiated less often after MOPPEBVCAD, but this regimen was more toxic. ABVD is still the best choice when it is combined with optional, limited irradiation.

scholarly journals Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

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