Rituximab Combined to ACVBP (R-ACVBP) Supported by Pegfilgrastim as a New Inductive Treatment Followed by High-Dose Consolidative Autotransplantation (HDC) for Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) in First-Line. Results of LNH 03–39B. A GELA Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3437-3437 ◽  
Author(s):  
Karim Belhadj ◽  
Jean-Philippe Jais ◽  
Pierre Feugier ◽  
Christian Gisselbrecht ◽  
Christian Recher ◽  
...  
Keyword(s):  
Single Dose ◽  
Response Rate ◽  
Complete Response Rate ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Free Survival ◽  
Cd34 Cells ◽  
Induction Regimen ◽  
Grade 3

Abstract ACVBP dose-intense induction regimen followed by HDC provides a better event-free survival and overall survival (OS) as compared to a conventional consolidative treatment in responding patients (pts) with aggressive lymphoma presenting with 2 or 3 factors of the age-adjusted International Prognostic Index (aa-IPI). However, complete response rate (CRR = CR+CRu) after ACVBP is not superior to 65%. Besides, it is established that Rituximab (R) combined with CHOP improves CRR and OS. Several controlled studies have demonstrated that a single dose of pegfilgrastim provides similar neutrophil recovery than filgrastim after chemotherapy in cancer patients. The main objective of this study was to evaluate the efficacy of a single dose of pegfilgrastim (6 mg) at d3 of the 4 cycles of R-ACVBP inductive regimen (rituximab 375 mg/m2 d1,doxorubicin 75 mg/m2 d1, cyclophosphamide 1,200 mg/m2 d1, vindesine 2 mg/m2, bleomycin 10 mg d1 and d5 and prednisone 60 mg/m2 d1-d5) delivered every 15 days in order to maintain an optimal combined dose intensity (CDI). CDI was defined as the minimum received dose intensities of doxorubicin and cyclophosphamide by each patient. Secondary objectives were to investigate if R combined to ACVBP translates into an improvement of CRR and progression free survival (PFS). The number of leukaphereses and CD34+ cells collected in responding pts were also analyzed. Responding pts received HDC with BEAM followed by stem cell rescue. From 01/2004 to 12/2005, 60 pts were enrolled: median age was 50 y (range: 21–60), 80% with aaIPI 2 and 20% with aa-IPI 3. The mean CDI was 89 (95% CI: 86–93), greater than theoretical cut-off of 85% (p=0.0017). After induction, 63% of pts achieved CR/CRu, 25% were in PR; 2 pts died during the induction phase. At least one episode of grade 3–4 neutropenia was observed in 98% of pts, 67% experienced grade 3–4 anemia, 38% thrombocytopenia and 73% febrile neutropenia. More than 2.106 CD34+ cells/kg were collected in 80% of the pts after the 3rd and/or 4th R-ACVBP while a collection failure was observed in 11 pts (20%), 7 of them being further collected with filgrastim. The median number of leukaphereses was 2. Among the 56 responding pts, 48 received HDC. With a median follow-up of 2 years, 2-year PFS was 71% (95% CI:61–84), and OS was 91% (95% CI:74–97). We conclude that CDI is satisfactory with pegfilgrastim support. R-ACVBP dose-intense induction regimen is feasible and safe on such high-risk pts but does not increase the complete response rate. However, PFS and OS seem encouraging; a longer follow-up is needed to see whether the addition of rituximab definitely contributes to decrease the relapse rate.

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.

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.

The VcR-CVAD Regimen Produces a High Complete Response Rate in Untreated Mantle Cell Lymphoma (MCL): First Analysis of E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for MCL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1661-1661 ◽  
Author(s):  
Brad S Kahl ◽  
Hailun Li ◽  
Mitchell R Smith ◽  
Randy D. Gascoyne ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Phase Ii ◽  
Research Funding ◽  
Response Rate ◽  
Complete Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 1661 Poster Board I-687 Introduction One approach to improving outcomes in Mantle Cell Lymphoma (MCL) is to incorporate newer targeted agents into standard chemotherapy regimens. As the proteasome inhibitor bortezomib (Velcade‘) achieved a 33% response rate in relapsed MCL, we hypothesized that the incorporation of Velcade (Vc) into a modified R-hyperCVAD chemotherapy backbone would result in a high complete response rate (CR). The new regimen, VcR-CVAD, was tested for safety and efficacy in a phase II study within the Wisconsin Oncology Network (UW) and demonstrated a CR rate of 77% (Kahl, ASH 2008). To determine the safety and efficacy of this regimen in a cooperative group setting, we initiated E1405: a phase II study of VcR-CVAD with maintenance rituximab (MR) for untreated MCL. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0-2, and adequate end organ function. The treatment plan included: Velcade 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1-3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1-2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1-4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients had an option to receive high dose chemotherapy and autologous stem cell transplantation (off protocol) rather than MR. The primary endpoint of the trial was the CR rate, incorporating PET imaging, to VcR-CVAD induction therapy. Results Seventy-six eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40-76), 59M:17F, 91% stage III/IV, and 39% with elevated LDH. Sixty-four patients (84%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), patient preference (2), and other/unknown (5). Response information is available on 74 patients while data is outstanding on 2 patients. The ORR was 96% (73/76; 95% CI, 89%-99%), CR rate 75% (57/76; 95% CI, 64%-84%) and the PR rate 21% (16/76; 95% CI, 13%-32%). Six of the PR patients were coded as such because of protocol violations in which a post-treatment bone marrow biopsy or PET scan was not obtained. The CR rate in the 68 completely restaged patients was 84%. Forty-four patients proceeded to planned MR while 21 patients went off protocol to SCT consolidation. Median follow up is currently too short (9 months) to assess PFS and OS. The major toxicity of the treatment regimen was expected myelosuppression. Grade 3-4 non hematologic toxicities were rare. No patients developed grade 3-4 neuropathy. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall response (96%) and CR rate (75%) in a representative MCL patient population treated on a cooperative group protocol. The CR rate was high and comparable to the UW pilot study (77%). No episodes of severe painful peripheral neuropathy were reported using the reduced vincristine dosage and the overall toxicity profile was very acceptable. Longer follow up is needed to determine if the high CR rate will translate into improved PFS and OS. Disclosures Kahl: Genentech: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as front line treatment in MCL. Smith:Genentech: Research Funding; Millennium: Research Funding. Advani:Seattle Genetics, Inc.: Research Funding. Horning:Genentech: Honoraria, Research Funding.

Pre-Phase Chemotherapy Followed By Ofatumumab (OFA) and Reduced Dose CHOP (OFA-mini-CHOP) for Patients over 80 Years with Diffuse Large B-Cell Lymphoma (DLBCL) – a Lymphoma Study Association (LYSA) Prospective Phase II Study (LNH09-7B)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3042-3042 ◽  
Author(s):  
Frédéric Peyrade ◽  
Bologna Serge ◽  
Vincent Delwail ◽  
Jean François Emile ◽  
Christian Rose ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Overall Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Significant Prognostic Factor ◽  
Free Survival ◽  
Grade 3

Abstract Introduction: R-miniCHOP is the standard chemotherapy for patients over 80 years (y) with DLBCL. In the LNH 03-7B trial, the 2-year overall survival was 58.9% [95% CI: 49.3-67.2%]. Grade III/IV toxicity and deaths occurred during the two first cycles mainly (Lancet Oncol. 2011 May;12(5):460-8). In order to improve overall survival (OS) rituximab (R) was replaced by Ofatumumab (OFA), a humanised anti-CD20 monoclonal antibody. In vitro data suggest that OFA induces more potent complement-mediated cytotoxicity than rituximab, and clinical data demonstrate activity of OF in rituximab-refractory lymphomas). In addition, to reduce early toxicity a pre-phase (PP) with vincristine and prednisone (P) was tested. Patients and methods: Patients older than 80 y with untreated CD20+ DLBCL, Ann Arbor stage I to IV, left ventricular ejection fraction > 50%, and a performance status (PS) of 0 to 4 were eligible. Patients received a PP with vincristine (1 mg TD D-7) and P (60 mg TD D-7 to D-4) before the first cycle of OF-miniCHOP. PP was followed by miniCHOP chemotherapy (cyclophosphamide: 400 mg/m² D1; doxorubicine: 25 mg/m² D1; vincristine: 1 mg total dose D1 and prednisolone 40 mg/m² by oral route from D1 to D5) plus OFA (1000 mg TD) every 21 days for 6 cycles. GCSF was optional. The primary objective was to evaluate the efficacy of PP OF-mini-CHOP as measured by the OS. Secondary endpoints were response rate (RR), progression free survival (PFS), event-free survival (EFS), disease-free survival (DFS) for complete responders and toxicities. Survival results are presented for all included patients on an intend-to-treat basis (n=120). Response to treatment was evaluated according to 1999 Cheson criteria. Results: From June 2010 to November 2011, One-hundred-twenty-patients (male, female) were included in 41 centers of the LYSA. The median age was 83 years (range 89-95). Seventy-seven percent of patients had a stage III/IV. LDH level was elevated in 58% of patients. Age-adjusted (aa) IPI was 2-3 in 57% of patients. One-hundred-twenty patients completed the PP, 107 the first three cycles and 89 received the whole regimen. For patients who started the first cycle, the mean relative Dose-Intensity during trial was 98%, 97% and 96 % for OFA, doxorubicine and cyclophosphamide respectively. Seventy-eight percent of patient received at least one injection of GCSF. The overall RR was 67.5%, including 35.8% of complete response and 20 % of unconfirmed complete response. At the time of this analysis, in September 2013, the median follow-up time was 26.6 months. The 2-year overall survival was 64.7% [95% CI: 55.3-72.7%]. The two-year PFS, EFS and DFS were 57.2% [95% CI: 47.7-65.6%], 53.1% [95% CI: 43.7-61.6%] and 66.6% [95% CI: 54.0-76.5%] respectively. Haematological toxicity was the most common side effect. Grade 3-4 neutropenia was observed in 20.8% of the patients and grade 3-4 thrombocytopenia in 1.7%. Seven patients (5.8%) experienced at least one episode of febrile neutropenia. Infusion reaction related to OFA was reported in 12.5% of patients. Prolonged hospitalization (> or = 10 days) was observed in 17 cases (14.1%) and mainly occurred during cycle 1 to cycle 3. Forty-five patients died during the treatment evenly distributed between lymphoma (62.2%), intercurrent and other causes (22.2%), and concurrent illness (15.6 %). No toxic death was reported. Six patients died during treatment (1 during PP, 4 during cycle 1 to cycle 3, 1 during cycle 4 to cycle 6) Thirty-nine patients died during follow-up. In univariate analysis, low aaIPI (0 /1) is the unique statistically significant prognostic factor of prolonged OS (OR 3.083, [1.458-6.517] CI95%). Instrumental Activities of Daily Living (IADL) score equal to 4 is associated with a longer PFS. By contrast, low Albuminemia level, undernutrition according to buzby index and high Charlson comorbidity index (CCI) were not predictive of survival. Conclusion: In DLCBL patients over 80 y, immunochemotherapy with PP OFA-mini-CHOP appears to be safe and effective, confirming that a substantial proportion of very old patients can be cured. The use of a PP seems to reduce the early death risk. OFA and PP seems to improve OS comparing with the previous reported data. The combination of a PP, monoclonal antibody against CD20 and miniCHOP can be the new standard regimen for DLBCL patients over 80 y. Disclosures Off Label Use: Use of ofatumumab in high grade lymphoma..

Cisplatin, Fluorouracil, and Leucovorin Induction Chemotherapy Followed by Concurrent Cisplatin Chemoradiotherapy for Organ Preservation and Cure in Patients With Advanced Head and Neck Cancer: Long-Term Follow-Up

2004 ◽  
Vol 22 (15) ◽  
pp. 3061-3069 ◽  
Author(s):  
A. Psyrri ◽  
M. Kwong ◽  
S. DiStasio ◽  
L. Lekakis ◽  
M. Kassar ◽  
...  
Keyword(s):  
Head And Neck ◽  
Induction Chemotherapy ◽  
Organ Preservation ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Advanced Head ◽  
Nasopharyngeal Tumors ◽  
Grade 3

Purpose The poor functional outcome in patients with advanced head and neck squamous cell carcinoma (HNSCC) with surgery and radiation has led to alternative approaches to advanced disease. We conducted a phase II study of induction chemotherapy followed by concurrent chemoradiotherapy for organ preservation in patients with advanced resectable and unresectable (nasopharyngeal) tumors. Patients and Methods Forty-two patients with stage III to IV resectable HNSCC and nasopharyngeal tumors received induction chemotherapy with two courses of cisplatin (20 mg/m2/d continuous infusion [CI]), fluorouracil (800 mg/m2/d CI), and leucovorin (500 mg/m2/d CI; PFL) for 4 days followed by concurrent therapy with cisplatin (100 mg/m2/d on days 1 and 22) and approximately 70 Gy of external-beam radiotherapy. Results Response to induction chemotherapy included partial response rate of 52% and complete response rate of 24%. The most common grade 3 or 4 toxicity was neutropenia (59%). After cisplatin chemoradiotherapy the complete response rate was 67%. Toxicities of cisplatin chemoradiotherapy consisted of grade 3 or 4 mucositis (79%) and neutropenia (51%). At a median follow-up of 71.5 months, 43% of the patients are still alive and disease-free. The 5-year progression-free survival (PFS) rate was 60%, and the 2- and 5-year overall survival (OS) rates were 67% and 52%, respectively. Three patients died of second primaries. Late complications of treatment included xerostomia and hoarseness. One patient had persistent dysphagia and required laser epiglotectomy 108 months after treatment. Conclusion Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS.

VcR-CVAD Produces a High Complete Response Rate in Untreated Mantle Cell Lymphoma: A Phase II Study from the Wisconsin Oncology Network

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 265-265 ◽  
Author(s):  
Brad Kahl ◽  
Julie Chang ◽  
Jens Eickhoff ◽  
Leslie Gilbert ◽  
Eric Rogers ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Complete Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
Complete Response ◽  
Mantle Cell ◽  
Induction Regimen ◽  
Grade 3

Abstract Introduction: There is no standard treatment for Mantle cell lymphoma (MCL). Intensive treatment strategies such as conventional R-hyperCVAD with alternating R-cytarabine/methotrexate or autologous stem cell transplant appear to improve PFS but the effect on OS is unclear. In addition, approximately 50% of newly diagnosed patients are not candidates for intensive therapies. Novel treatment strategies are needed. We have published the results of a study using a modified R-hyperCVAD induction followed by maintenance rituximab (Kahl et al, Ann Oncol 2006). This induction strategy yielded a complete response (CR) rate of 64% and the entire treatment program yielded a median PFS of 37 months. Bortezomib (Velcade) has demonstrated promising activity in relapsed MCL (Fisher et al, J Clin Onc, 2006). We hypothesized that the incorporation of Velcade (Vc) into the induction regimen would improve the CR rate. The new regimen, VcRCVAD, was tested for safety and efficacy in a phase II study at the University of Wisconsin and within the Wisconsin Oncology Network. Methods: Eligible patients had histologically confirmed mantle cell lymphoma, PS 0–2, and adequate end organ function. The final treatment plan included: Velcade 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1–3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1–2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1–4. Due to excessive painful peripheral neuropathy (PN), 2 dose modifications were required during the course of the study. Patients 1–7 received 1.5 mg/m2 Velcade and 2 mg vincristine. Patients 8–14 received 1.3 mg/m2 Velcade and 2 mg vincristine. Patients 15–30 received 1.3 mg/m2 Velcade and 1 mg vincristine. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF cytokine support. Patients achieving at least a PR receive maintenance rituximab therapy for 5 years. Results: Enrollment is complete and all 30 patients are evaluable for response to VcRCVAD induction. Baseline characteristics include median age 60.5 (48–74), 24M:6F, 26/30 (87%) stage IV, and 12 (40%) low-risk, 8 (27%) int-risk, and 10 (33%) high-risk by MIPI. 3 patients (10%) experienced PD during induction therapy and 27 (90%) responded with 23 CR/CRu (77%) and 4 PR (13%). With a median follow up of approximately 18 months, the 18-month PFS and OS are 73% and 97%, respectively. The major toxicity of this treatment regimen is painful PN and expected hematologic toxicity. 5/7 patients in cohort 1 and 3/7 patients in cohort 2 developed grade 3 painful PN and 1 patient in cohort 2 developed grade 4 painful PN. Only 1/16 patients in the final cohort experienced grade 3 painful PN. All neuropathy eventually improved to ≤ grade 2, but 10 patients require chronic medication for symptom relief. 13/167 (8%) of the treatment cycles were complicated by neutropenic fever/infection. There were no treatment related deaths. Conclusion: The VcR-CVAD induction has produced high overall response (90%) and CR rate (77%) in a very representative MCL patient population. Comparing these data to our previous frontline MCL study, the CR rate appears to be enhanced (77% vs 64%) by the addition of Velcade. Longer follow up is needed before determining if the higher CR rate will translate into an improved PFS and OS. Because of the risk for painful PN, caution must be exercised when using vincristine and Velcade in combination. The MTD for this combination was 1 mg vincristine and 1.3 mg/m2 Velcade. The encouraging complete response rate provided the rationale for ECOG study E1405, which is testing the safety and efficacy of this induction regimen in a cooperative group setting.

Treatment of Indolent Lymphomas with 3 CNOP- 4 COPB.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4594-4594
Author(s):  
Edgar Murillo ◽  
Maria Nambo ◽  
Agustin Aviles ◽  
Natividad Neri ◽  
Alejandra Talavera ◽  
...  
Keyword(s):  
Response Rate ◽  
Chemotherapy Regimen ◽  
Disease Free Survival ◽  
Complete Response ◽  
Bulky Disease ◽  
Free Survival ◽  
Grade 3 ◽  
Indolent Lymphomas ◽  
Disease Free

Abstract Frequently recurrences and progressive resistance to chemotherapy characterize indolent lymphomas. The use of anthracyclines has been improved the response rate and the disease free survival, however, its use in elderly patients is controversial because the related toxicities. We analyze the use of a chemotherapy regimen with a short course of anthracycline. Material and Methods: We included patients with untreated indolent lymphomas according to the WHO classification. The chemotherapy regimens were 3 cycles of CNOP (cyclophosphamide 600 mg/m2 day 1, mitoxantrone 10 mg/m2 day1, vincristine 1.4 mg/m2 day 1 and prednisone 50 mg/m2 days 1–5) every 21 days, followed by 4 cycles of COPB (cyclophosphamide 800 mg/m2 day 1, vincristine 1.4 mg/m2 day 1, a bleomycin 10 U/m2 day 1 and prednisone 50 mg/m2 days 1–5) every 14 days. Results: In an intent to treat 75 patients were valuable, 37 females and 38 males, median age was 56 (range 28–84), the histological variants were: follicular grade 1 and 2 (45 patients), lymphoma/leukemia of small well differentiated lymphocytes (6 patients), mantle cell lymphoma (1 patient), nodal marginal zone lymphoma (4 patients), lymphoplasmocytic lymphoma (1 patient), indolent lymphoma not otherwise characterized (12 patients), 61 patients (81.3%) had bulky disease, 57 patients (76%) had advanced disease (stage III and IV). According to the IPI: low risk (28 patients), low intermediate (21 patients), high intermediate (14 patients), and high (12 patients). A total of 488 cycles were administrated, 82 (16.8%) cycles had hematologic toxicities: 30 cycles grade 1, 29 cycles grade 2, 18 cycles grade 3, and 5 cycles grade 4. Filgrastim was needed in 20 patients (43 cycles). 58 patients had gastrointestinal toxicity (29 grade1, 26 grade 2, 3 grade 3), 61 patients had neurological toxicity (47 grade 1, 13 grade 2, 1 grade 3). 14 patients (18.7%) required hospitalization, 7 patients due to toxicity related chemotherapy and 6 due to tumor progression. The overall response rate was 84% (63 patients): Complete response 33 patients (44%), unconfirmed complete response 6 patients (8%), partial response 24 patients (32%). Failure to treatment occurred in 11 patients (14.7%). Adding radiotherapy 12 more patients were converted to complete response for a total of 45 patients (60%). With a median of follow up of 24 months (range 3–62 months) 10 patients (13.3%) relapsed, 13 (17.3%) patients died (8 due to tumor progression and 3 related to toxicity of the regimen). The actuarial 5-year disease free survival was 71% and the overall survival 86%. Conclusions: This chemotherapy regimen provides an effective alternative for the treatment of indolent lymphomas even in advanced or bulky disease. This regimen is well tolerated for elderly patients and has a good safety profile. It is necessary a long time of follow up to establish the importance of the regimen in free disease survival and in overall survival.

Rituximab and Reduced Dose CHOP (R-mini-CHOP) for Patients Over 80 Years with Diffuse Large B-Cell Lymphoma (DLBCL) – Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study LNH03-7B

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 853-853 ◽  
Author(s):  
Frederic Peyrade ◽  
Fabrice Jardin ◽  
Christian Gisselbrecht ◽  
Antoine Thyss ◽  
Jean François Emile ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Performance Status ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Albumin Level ◽  
Old Patients ◽  
Free Survival ◽  
Grade 3

Abstract Abstract 853 Introduction: Half of the cases of DLBCL occurs in patients over 65 years but very few data are available for patients over 80 years. These older patients however seem to respond as younger patients when treatment can be tolerated. In the aim to evaluate tolerance and efficacy of a reduced dosage chemotherapy regimen associated with rituximab in this population, the GELA initiated in 2005 a prospective, multicenter, phase II study. Patients and methods: Patients older than 80 years with untreated CD20+ DLBCL, Ann Arbor stage I with bulky mass to IV and a performance status (PS) of 0 to 2 were eligible. Patients were treated with mini-CHOP chemotherapy (cyclophosphamide: 400 mg/m2 D1; doxorubicine: 25 mg/m2 D1; vincristine: 1 mg total dose D1 and prednisolone 40 mg/m2 by oral route from D1 to D5) plus rituximab (375 mg/m2 D1) every 21 days for 6 cycles. GCSF was optional. The primary objective was to evaluate the efficacy of R-mini-CHOP as measured by the overall survival. Secondary endpoints were response rate, progression free survival (PFS), event-free survival (EFS), disease-free survival (DFS) for complete responders and toxicities. Survival results are presented on an intend-to-treat basis. Response to treatment was evaluated according to 1999 Cheson criteria. Results: One-hundred-and-fifty-patients (51 male, 99 female) were included in 38 centers of the GELA. The median age was 84 years (range 80–95). Seventy-five percent of patients had a stage III/IV. LDH level was elevated in 69% of patients. Age-adjusted (aa) IPI was 2–3 in 66% of patients. One-hundred-twenty-nine patients completed the first three cycles and 108 received the whole regimen. The Dose-Intensity for patients who completed the three first cycle was 100% and 96.8% for doxorubicine and cyclophosphamide respectively. Thirty-six percent of patient received at least one injection of GCSF. The overall response rate was 74%, including 40% of complete response and 23% of unconfirmed complete response. At the time of this analysis, in July 2010, the median follow-up time was 20 months. The 2-year overall survival was 58.9% [95% CI: 49.3–67.2%]. The two-year estimated PFS, EFS and DFS were 47.4% [95% CI: 38.1–56.2%], 44.8% [95% CI : 35.7–53.6%] and 56.6% [95% CI : 49.3–67.2%] respectively. Hematological toxicity was the most common side effect. Grade 3–4 neutropenia was observed in 39% of the patients and grade 3–4 thrombocytopenia in 7%. Eleven patients (7%) experienced at least one episode of febrile neutropenia. Overall patients experienced a median of 4 nights of hospitalization during treatment phase (range 0–46). Thirty patients died during the treatment evenly distributed between treatment toxicity (6.7%) lymphoma (6.7%) and intercurrent causes (6.7%). In a univariate analysis, PS 0 or 1, aaIPI 0 or 1, number of extra-nodal sites <2, albumin level >35g/l, mass <10cm and a high IADL (Instrumental activities of daily living) score appear to be highly predictive of a prolonged survival. In a multivariate analysis a PS equal to 0 or 1 and an albumin level >35 g/l were significantly associated with a longer survival. Conclusion: In patients over 80 years with DLBCL and a good performance status, immunochemotherapy with R-mini-CHOP appears to be safe and effective, indicating that a substantial proportion of very old patients could indeed be cured. This regimen could be considered as a platform for the introduction of new drugs in the first line treatment of this population. Disclosures: No relevant conflicts of interest to declare.

Evaluation of R-CHOP and R-CVP in the treatment of elderly patient with non-Hodgkin lymphoma

MedPharmRes ◽  
2019 ◽  
Vol 3 (3) ◽  
pp. 1-6
Author(s):  
Truc Phan ◽  
Tram Huynh ◽  
Tuan Q. Tran ◽  
Dung Co ◽  
Khoi M. Tran
Keyword(s):  
Elderly Patients ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
The Elderly ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Common Sign ◽  
Related Mortality

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.

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.

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