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.

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

scholarly journals Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

2021 ◽  
Author(s):  
Pavani Chalasani ◽  
Kiah Farr ◽  
Vicky Wu ◽  
Isaac Jenkins ◽  
Alex Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Peripheral Neuropathy ◽  
Clinical Benefit ◽  
Low Dose ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

scholarly journals Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

2020 ◽  
pp. JCO.20.02259
Author(s):  
Paul G. Richardson ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Bladé ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

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.

Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Sara Lonardi ◽  
Vittorina Zagonel ◽  
Eric Van Cutsem ◽  
M. Luisa Limon ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Therapy Option ◽  
Grade 3

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]

scholarly journals Association between neutropenia and survival to nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Giandomenico Roviello ◽  
Monica Ramello ◽  
Martina Catalano ◽  
Alberto D’Angelo ◽  
Raffaele Conca ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Response Rate ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Common Side Effect ◽  
First Line ◽  
Free Survival ◽  
Grade 3 ◽  
Toxicity Criteria

Abstract Neutropenia is a common side effect associated with nab-paclitaxel gemcitabine (Nab-Gem) therapy. We retrospectively investigated the association between neutropenia induced by first-line Nab-Gem and survival in metastatic pancreatic carcinoma patients. Metastatic pancreatic patients treated with first-line Nab-Gem were included in this retrospective analysis. Neutropenia was categorized using the National Cancer Institute Common Toxicity Criteria scale. Outcome measures were overall survival (OS), progression-free survival (PFS) and response rate. 115 patients were analyzed. Median PFS was 7 months (95% CI 5–8) for patients with grade ≥ 3 neutropenia and 6 months (95% CI 5–6) for patients with grade < 3 neutropenia [p = 0.08; hazard ratio (HR 0.68)]. Median OS was 13 months (95% CI 10–18) for patients with grade ≥ 3 neutropenia and 10 months (95% CI 8–13) for patients with grade < 3 neutropenia (p = 0.04; HR 0.44). In multivariate analysis, the occurrence of grade ≥ 3 neutropenia showed a statistically significant association with OS (HR 0.62; 95% CI 0.09–0.86; p = 0.05). Nab-Gem-induced neutropenia is associated with longer survival in metastatic pancreatic cancer patients.

Topotecan and etoposide as salvage chemotherapy in patients with irinotecan- and platinum-failed small-cell lung cancer: A phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18177-18177
Author(s):  
H. Choi ◽  
B. Choi ◽  
S. Shin ◽  
S. Cheon ◽  
S. Cheon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Median Progression Free Survival ◽  
Grade 3

18177 Background: The efficacy and safety of a combined regimen of topotecan and etoposide was tested in patients with relapsed or refractory small-cell lung cancer. Methods: From October 2003 to May 2005, 23 patients who have failed to the previous irinotecan and platinum chemotherapy received intravenous topotecan 1mg/m2 (day 1–5) followed by intravenous etoposide 80mg/m2 (day 1–3). Treatment was repeated every 21 days for a maximum of 6 cycles. Results: Twelve patients were refractory to first-line chemotherapy. Seventeen patients (73.9%) were male and the median age was 63 years. ECOG performance status was 0–1 in 13 (56.5%) patients. The median cycles of chemotherapy was 3. Twenty one patients were assessable for response evaluation. The overall response rate was 17.4% (0 CR, 4 PR, 7 SD, 10 PD) under the intent-to-treat analysis. After a median follow- up of 20.8 months, median progression free survival was 4.7 months and median overall survival was 9.5 months. The estimated 1-year survival rate was 38.7%. In sensitive relapsed patients, 2 achieved tumor response and median progression free survival and overall survival were 5.5 months and 14.5 months. All patients were assessable for toxicity and major toxicities were myelosuppression. Grade 3/4 neutropenia and thrombocytopenia occurred in 18 (78.3%) and 12 (52.2%) patients, respectively. Grade 3/4 febrile neutropenia occurred in 2 patients (8.7 %) and infection in 3 patients (13.0%). There was one treatment-related death due to pneumonia. Conclusions: This salvage regimen failed to demonstrate a considerable response rate compared with monotherapy for relapsed or refractory SCLC. However, the combination of topotecan and etoposide could be further studied for sensitive relapsed patients pretreated with irinotecan and platinum No significant financial relationships to disclose.

A Phase I/II Study of the Tolerability of Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients with Impaired Renal Function: Pre1003, a Precog LLC Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1856-1856
Author(s):  
Joseph R. Mikhael ◽  
Judith Manola ◽  
Amylou Constance Dueck ◽  
Suzanne R Hayman ◽  
Kurt Oettel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Impaired Renal Function ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Previously Treated ◽  
Grade 3

Abstract Abstract 1856 Background: Lenalidomide has proven to be a highly effective treatment in relapsed multiple myeloma (MM), particularly when used in combination with dexamethasone. However, over 30% of patients with myeloma have renal insufficiency and as lenalidomide is renally excreted, little information is available about its use in myeloma patients with impaired kidney function. Defining a safe and effective dose of lenalidomide in this context is critical. Objective: We undertook this study to establish the maximum tolerated dose of lenalidomide in three cohorts of patients with different levels of impaired renal function: Group A - patients with creatinine clearance (CrCl) between 30 and 60 mL/min, Group B - patients with CrCl <30 mL/min not on dialysis, and Group C - patients with CrCl < 30mL/min who are on dialysis. Secondary endpoints included response rate, progression free survival and overall survival. Methods: Eligible patients had previously treated MM with renal impairment defined as creatinine clearance < 60 mL/min measured within 21 days prior to registration. Patients previously treated with lenalidomide were required to demonstrate clinical response (any duration) or stable disease with progression-free interval of > 6 months from start of that therapy. All patients received dexamethasone 40 mg orally on days 1, 8, 15 and 22 of a 28-day cycle. Prophylactic anticoagulation consisted of either 81 mg or 325 mg per day of aspirin. Patients also received lenalidomide orally every 1 or 2 days on days 1 through 21 of a 28-day cycle, as described below (Table 1). Starting doses were as in US Product Insert. Dose escalation follows a standard 3+3 design. Results: There have been 23 patients enrolled into groups and cohorts as shown in Table 1. Median age was 73 (range 49–89) and 13 (57%) were women. ISS stage was advanced in all patients, 0 in stage 1, 4 (18%) in stage 2 and 19 (82%) in stage 3. The regimen was well tolerated. Indeed, the MTD has not been reached in any of the groups, as no DLTs have occurred to date. The most commonly reported clinical adverse events (all grades, independent of attribution) across all patients included infections, hyperglycemia, constipation, dizziness, hyponatremia, hypocalcemia and tremor. Hematological toxicities (grade 3–4) occurred in 13 out of 21 pts (62%), mostly neutropenia and thrombocytopenia. Grade 3–4 events at least possibly related to the regimen occurred in 70% and included pneumonia (26%) and otitis media (9%). Response was seen in 14 patients, resulting in an overall response rate of 61%. CR was seen in 1 patient (4%), VGPR in 2 patients (9%), PR in 11 patients (43%), and SD for 9 patients. With median follow-up of 15.5 months, median progression-free survival is 9.8 months and median overall survival is 22 months. Conclusion: Lenalidomide and dexamethasone is a safe and effective regimen in patients with multiple myeloma and renal insufficiency. It is also very well tolerated, although cytopenias are common but manageable. MTD has yet to be reached in each group, allowing for higher doses to be given than previously thought, including 25mg daily (for 21/28 days) in patients with CrCl 30–60 mL/min, 25 mg every other day (for 21/28 days) in patients with CrCl < 30 mL/min not on dialysis, and 10mg daily (for 21/28 days) in patients with CrCl < 30 mL/min on dialysis. These results will provide needed, clinically relevant dosing for lenalidomide in MM patients with renal insufficiency. Disclosures: Kaufman: Millenium: Consultancy; Onyx: Consultancy; Celgene: Consultancy; Novartis: Consultancy.

Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma

Blood ◽  
2006 ◽  
Vol 109 (7) ◽  
pp. 2767-2772 ◽  
Author(s):  
Antonio Palumbo ◽  
Maria Teresa Ambrosini ◽  
Giulia Benevolo ◽  
Patrizia Pregno ◽  
Norbert Pescosta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rate ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Free Survival ◽  
Grade 3 ◽  
Dose Levels ◽  
Initial Results

AbstractIn multiple myeloma (MM), the addition of thalidomide or bortezomib to the standard oral melphalan/prednisone combination significantly increased response rate and event-free survival. In this multicenter phase 1/2 trial, dosing, safety, and efficacy of the 4-drug combination, bortezomib, melphalan, prednisone, and thalidomide (VMPT) was determined. Bortezomib was administered at 3 dose levels (1.0 mg/m2, 1.3 mg/m2, or 1.6 mg/m2) on days 1, 4, 15, and 22; melphalan was given at a dose of 6 mg/m2 on days 1 through 5 and prednisone at 60 mg/m2 on days 1 through 5. Thalidomide was delivered at 50 mg on days 1 through 35. Each course was repeated every 35 days. The maximum tolerated dose of bortezomib was 1.3 mg/m2. Thirty patients with relapsed or refractory MM were enrolled; 20 patients (67%) achieved a partial response (PR) including 13 patients (43%) who achieved at least a very good PR. Among 14 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 nonhematologic adverse events included infections (5 patients), fatigue (1), vasculitis (1), and peripheral neuropathy (2); no grade 4 toxicities were recorded. Initial results showed that VMPT is an effective salvage therapy with a very high proportion of responses. The incidence of neurotoxicities was unexpectedly low.

Bortezomib, Bendamustine, and Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma: The Phase II VERTICAL Study

2011 ◽  
Vol 29 (25) ◽  
pp. 3389-3395 ◽  
Author(s):  
Nathan Fowler ◽  
Brad S. Kahl ◽  
Peter Lee ◽  
Jeffrey V. Matous ◽  
Amanda F. Cashen ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
International Workshop ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Free Survival ◽  
Highly Active ◽  
Grade 3

Purpose The aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment. Patients and Methods Patients received five 35-day cycles of bortezomib, bendamustine, and rituximab: bortezomib administered intravenously (IV) at a dose of 1.6 mg/m2 on days 1, 8, 15, and 22, cycles one to five; bendamustine 50, 70, or 90 mg/m2 IV over a 60-minute infusion on days 1 and 2, cycles one to five; and rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle one and day 1 of subsequent cycles. Patients were assessed using the International Workshop Response Criteria, with the primary end point of 60% complete response rate. Results Seventy-three patients were enrolled. During the dose-escalation phase, the maximum-tolerated dose for bendamustine was not reached; the 90 mg/m2 dose level was expanded for the efficacy assessment, and a total of 63 patients received bendamustine 90 mg/m2. In these 63 patients, the overall response rate was 88% (including 53% complete response). Median duration of response was 11.7 months (95% CI, 9.2 to 13.3). Median progression-free survival was 14.9 months (95% CI, 11.1 to 23.7). Toxicities were manageable; myelosuppression was the main toxicity (25% and 14% of patients experienced grade 3 to 4 neutropenia and grade 3 to 4 thrombocytopenia, respectively). Transient grade 3 to 4 neuropathy occurred in 11% of patients. Conclusion The combination of bortezomib, bendamustine, and rituximab is highly active in patients with follicular lymphoma who have received previous treatment.

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