Can a Dose-Dense RCHOP-Like Regimen Be Effectively Used In a Community Setting? Results of a Phase II Study Employing Pegylated Liposomal Doxorubicin In Elderly (> age 60) or Cardiac Compromised (LVEF <45%) Patients with Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2797-2797
Author(s):  
Stephen J. Noga ◽  
Judith Bosley ◽  
Pamela Nickoles
Keyword(s):  
Phase Ii ◽  
Survival Data ◽  
Research Funding ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Dose Dense

Abstract Abstract 2797 Chemotherapy employing the RCHOP every 21 day regimen has become the standard of care for patients with DLBCL. Although the GELA study did include older patients, NHL incidence rises more steeply with age, with a third of cases occurring in patients over 75 years of age. Community oncologists see an ever-increasing NHL age group with multiple co-morbidities. There is also debate whether DLBCL is more aggressive/chemo-resistant at the higher age range. For many, cardiac issues exclude them from an adriamycin-based regimen and possible cure. Since pegylated liposomal doxorubicin (PLD) has a reported lower cardiac toxicity profile even at higher overall doses than doxorubicin, it was substituted into a dose-dense RCHOP regimen. To this end, we developed a phase II dose-dense/dose escalation study of PLD (Doxil®,20 mg/m2: cohort I, 25 mg/m2: cohort II, 30 mg/m2: cohort III), cyclophosphamide (CY, 750 mg/m2), vincristine (1.4 mg/m2: 2 mg max), prednisone (100 mg PO days 1–5) and rituximab (375 mg/m2) on day 1 followed by pegfilgrastim (Neulasta®, 6 mg, SC) on day 2 of a 14 day cycle. Patients received a planned 6 cycles of chemotherapy or 2 cycles past best response. Patients >60 years or with left ventricular ejection fractions (LVEF) <45% were enrolled with ECOG performance status (PS) of 0 – 3. Three, 6 and 8 patients (17 total) were enrolled on cohorts I – III, respectively, Intent to treat (ITT) data included all patients. Response/survival data excluded 2 patients who deteriorated by start of cycle 1 chemotherapy. Safety and SAE's were assessed with each cohort. Quantitative LVEF was obtained with each cycle, CT's every 3 cycles and PET/CT at baseline and within 60 days of chemotherapy completion. Median age was 78 (62-87), 59% were female and baseline LVEF from 12% (with AICD but ECOG PS1) to 87% (median 60%). There was no reduction in LVEF for patients receiving >1 cycle of chemotherapy. Patients who were hospitalized (PS>2) or who's PS declined rapidly between study entry and cycle 1 initiation rapidly became too moribund to complete planned therapy. Relative dose intensity [RDI: (delivered chemotherapy/time to complete)/(planned chemotherapy/planned time to complete)] for the entire group averaged 96 (83 – 100)% for PLD, median 100%, and 97 (86 – 100)%, median 100%, for cyclophosphamide. Nearly all patients (92%) achieved a CR/nCR with a 77% CR rate. Despite an every 14 day anthracycline regimen, Grade >2 hematologic toxicities were manageable and others were low. Overall Survival in the ITT population was 65% and 37% at 12 and 24 months, respectively. Censoring for patients removed in or after cycle 1 yielded a survival rate of 73% at 12 months and 42% at 24 months. This elderly patient population had significant long term morbidities, post-chemotherapy, leading to mortality from cardiac disease, ARF and liver failure besides lymphoma related causes. Adjusting for the non-lymphoma deaths gave adjusted survivals of 85% and 71% at 12 and 24 months, respectively. We conclude that it is feasible to deliver a dose-dense anthracycline regimen to geriatric patients with acceptable toxicity. Indeed, 71% of study patients were ≥ 70 years and 47% were ≥ 80 years. Microarray analysis may pinpoint which elderly patients may require a more intensive regimen to effect cure. Grade (%) N F/N Hosp F/N Tpenia PPE Cardiac Stomatitis All 88 24 24 82 65 24 47 3 24 12 12 24 6 12 6 4 41 12 12 6 6 - - Neutropenia =N, Febrile Neutropenia =F/N, Hospitalization for F/N = Hosp F/N, Thrombocytopenia = Tpenia, Palmar- Plantar erythrodysesthesia = PPE Disclosures: Noga: Amgen: Honoraria, Research Funding, Speakers Bureau, none; Millenium Takada: Consultancy, Honoraria, Research Funding, Speakers Bureau, none; Ortho-Centicor: Research Funding, Speakers Bureau, none; Cephalon: Honoraria, Speakers Bureau, none; Pfizer: Speakers Bureau, none; Cellgene: Honoraria, Research Funding, Speakers Bureau, none. Off Label Use: Doxil (pegylated liposomal doxorubicin) in place of adriamycin in a CHOP-R regimen for DLBCL.

Safety analysis of a phase II study of cyclophosphamide, vincristine, non-pegilated liposomal doxorubicin (Myocet), and prednisone + rituximab in biweekly regimen (R-COMP-14) as primary treatment of non-Hodgkin lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17532-17532 ◽  
Author(s):  
F. R. Garcia Arroyo ◽  
J. Herrero ◽  
M. Provencio ◽  
J. Gómez-Codina ◽  
A. Rueda ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
Safety Analysis ◽  
Non Hodgkin Lymphoma ◽  
Dose Dense

17532 Background: Gold standard treatment of CD20+ aggressive B-cell non-Hodgkin lymphoma, R-CHOP, has been suggested to improve outcome when administered as dose-dense regimen supported with G-CSF. The non-pegylated liposomal doxorubicin (Myocet) has an improved safety profile compared to standard formulations of doxorubicin. Standard R-CHOP regimen has been modified replacing doxorubicin with Myocet, administered on a biweekly basis (R-COMP-14) looking for an increase in efficacy without impairing tolerability Methods: Single arm, multicentric, 2-step (Simon design) phase II trial. Newly diagnosed, diffuse large B-cell lymphoma, stages III, IV or I, II with IPI ≥ 1, CD20+, eligible patients (Pt) were treated with Myocet 50 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2 (max. 2 mg), rituximab 375 mg/m2 and prednisone 100 mg/d d1–5 in biweekly cycles. Pegilated filgastrim (Neulasta™) was administered on day 2 of the cycle. Response was assessed after 3 cycles, and patients with PR or CR received 5 additional cycles. A safety analysis was planned by protocol with data of first patients included Results: The median age of the 13 Pt included was 59 (range 28–64). At baseline 53.9% Pt had III-IV stage and 41.7% had extraganglionar involvement. Median basal LVEF was 66% (range 44–79). A median of 7 cycles of R-COMP were administered. The median relative dose intensity per week for Myocet was 94.9%. 6.2% of the cycles were delayed and 8.6% of the cycles were dose reduced. There were 2 episodes of febrile neutropenia. G3 asthenia, G3 neurotoxicity and G3 related infection were found in one cycle each. One patient had G3 hepatic toxicity resolved with dose reduction. At the end of treatment the median LVEF was 65.52% (range 52–76), there was no cardiac event related to the treatment. 84.6% of Pt had complete or partial response (7 RC, 2 uRC, 2 PR, 1 SD, 1 PD) at the end of the study Conclusions: In this small safety group of Pt that received the dose-dense regimen, the preliminary results suggest that R-COMP-14 supported with Neulasta is a well tolerated and effective regimen. Recruitment will proceed as planned (75 Pt). No significant financial relationships to disclose.

Pegylated Liposomal Doxobubicin (PLD) Can Be Escalated in a Dose-Dense, 14 Day CDOP-Rituximab Regimen without Affecting Relative Dose Intensity (RDI) in Patients with Diffuse Large B Cell Lymphoma (DLBCL) Who Are Elderly or Have Compromised Cardiac Status.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2692-2692
Author(s):  
Stephen J Noga ◽  
Judy Bosley ◽  
Pamela Nickoles ◽  
Pallavi Kumar ◽  
Erica Monfred
Keyword(s):  
Cardiac Function ◽  
Dose Intensity ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Poor Performance Status ◽  
Term Survival ◽  
Full Dose ◽  
Dose Dense

Abstract Abstract 2692 Poster Board II-668 Anthracycline/rituximab based chemotherapy such as CHOP-R has become the standard of care for DLBCL where cure is the primary goal. There is a direct correlation between long term survival and the delivery of on time, full dose chemotherapy. Several studies in DLBCL now indicate that this concept of dose intensity may be further exploited by compacting therapy cycles from the usual 21 days to the 14 day “dose dense” regimens. It is hoped that this will result in higher cure rates. Community oncologists often face tough decisions when deciding how to treat the increasing numbers of DLBCL patients who are elderly and have multiple co-morbidities including declining cardiac function and poor performance status (PS). Since PLD has a reported lower cardiac toxicity profile even at higher overall doses than doxorubicin, it was substituted into a dose-dense CHOP-R regimen. Patients >60 years or with left ventricular ejection fractions (LVEF) <45% were enrolled in a phase II dose escalation study of PLD (Doxil*®,20 mg/m2: cohort I, 25 mg/m2: cohort II, 30 mg/m2: cohort III), cyclophosphamide (CY, 750 mg/m2), vincristine (1.4 mg/m2: 2 mg max), prednisone (100 mg PO days 1-5), rituximab (375 mg/m2) on day 1 followed by pegfilgrastim (6 mg, SC) on day 2 of a 14 day cycle. Patients received a planned 6 cycles of chemotherapy or 2 cycles past best response. Safety and SAE's were assessed with each cohort or every 6 patients. Quantitative LVEF was obtained with each cycle, CT's every 3 cycles and PET/CT at baseline and within 60 days of chemotherapy completion. Median age was 76 (62-87) years, 59% were female with baseline LVEF from 12% (with AICD but ECOG PS1) to 75% (PS3). There was no diminution in LVEF for patients receiving >1 cycle of chemotherapy. AE's >grade 2 were neutropenia/fever (n=3), neutropenia (n=1), thrombocytopenia (n=1), chest pain (n=1), hyperglycemia (n=2), CHF (n=1) and worsening pleural effusion (n=1). PPE related to PLD was manageable and minimally delayed therapy. . Patients who were hospitalized (PS >2) or who's PS declined rapidly between study entry and cycle 1 initiation rapidly became too moribund to complete planned therapy. Escalation of the PLD dose from 20 mg/m2 to 30 mg/m2 did not alter the ability to deliver on time, full dose chemotherapy. Decreasing cycle length to 2 weeks actually increased the RDI to 150% over the standard 3 week regimen. This may be beneficial in the elderly where it is still uncertain if lower survival is due to substandard treatment regimens or a more chemo-resistant NHL phenotype. In the first 12 evaluable patients completing full course chemotherapy, 10 patients were in CR (CR +nCR), and 1 in PR within 60 days of chemotherapy completion. At 1 year, 6 patients were in CR and 2 had progressive disease. We conclude that CDOP-R 14 warrants further study in the elderly population and in those DLBCL patients with compromised cardiac function. Disclosures: Noga: Tibotec, Inc: Honoraria, Research Funding, Speakers Bureau; Amgen, Inc: Honoraria, Speakers Bureau. Off Label Use: Doxil. Substitutes for the standard anthracycline, doxorubicin, in the CHOP regimen for agressive NHL.

Pegylated Liposomal Doxorubicin and Trastuzumab in HER-2 Overexpressing Metastatic Breast Cancer: A Multicenter Phase II Trial

2006 ◽  
Vol 24 (18) ◽  
pp. 2773-2778 ◽  
Author(s):  
Stephen Chia ◽  
Mark Clemons ◽  
Lee-Ann Martin ◽  
Angela Rodgers ◽  
Karen Gelmon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her 2 ◽  
Grade 3

Purpose Cardiotoxicity precludes the concurrent use of doxorubicin and trastuzumab. Because pegylated liposomal doxorubicin (PLD) has equal efficacy but significantly less cardiotoxicity than conventional doxorubicin, this phase II study assessed the rate of cardiotoxicity and efficacy of first-line PLD plus trastuzumab in HER-2–positive metastatic breast cancer (MBC). Patients and Methods Women with HER-2–positive, measurable MBC, and a baseline left ventricular ejection fraction (LVEF) ≥ 55% were treated with PLD 50 mg/m2 every 4 weeks for six cycles and weekly trastuzumab (4 mg/kg loading dose then 2 mg/kg thereafter). Cardiotoxicity was defined as symptomatic congestive heart failure (CHF) with ≥ 10% decline in LVEF to below lower limits of normal, ≥ 15% decline in LVEF without symptomatic CHF, or less than 10% LVEF decline to less than 45%. Results Thirty women were enrolled, 13 had received prior adjuvant anthracyclines. A median 5.5 cycles of PLD were administered. Mean baseline LVEF was 62.8%, 59.5% after cycle four, and 58.3% after cycle six. Three patients (10%) developed protocol-defined cardiotoxicity. No patients developed symptomatic CHF. Response rate was 52%, with an additional 38% stable disease rate. At a median follow-up of 13.9 months, the median progression-free survival was 12.0 months; median overall survival has not yet been reached. The most common adverse events were grade 3 hand-foot syndrome (30%) and grade 3/4 neutropenia (27%). Conclusion The combination of PLD and trastuzumab is a well tolerated and active regimen in HER-2-positive MBC. Cardiotoxicity was observed, but limited to asymptomatic declines in LVEF. Further evaluation of this combination is warranted.

Phase II Study of Pegylated Liposomal Doxorubicin in Combination With Gemcitabine in Patients With Metastatic Breast Cancer

2003 ◽  
Vol 21 (17) ◽  
pp. 3249-3254 ◽  
Author(s):  
Edgardo Rivera ◽  
Vicente Valero ◽  
Banu Arun ◽  
Melanie Royce ◽  
Rosni Adinin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Median Response

Purpose: We conducted a phase II clinical trial to determine the clinical efficacy and safety of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. Patients and Methods: Patients were eligible if they had measurable disease, no prior chemotherapy for metastatic disease, and a performance status ≤ 2 on the Zubrod scale. Patients received pegylated liposomal doxorubicin 24 mg/m2 intravenously on day 1, plus gemcitabine 800 mg/m2 intravenously on days 1 and 8 of each 21-day cycle. Results: Of 49 patients enrolled, 27 had received prior adjuvant chemotherapy (19 with an anthracycline). Prior median cumulative anthracycline dose was 240 mg/m2. In total, three complete responses and 21 partial responses were achieved in 46 assessable patients, for an overall response rate of 52% (95% confidence interval, 37% to 67%). Responses were observed in 11 (58%) of 19 patients with previous anthracycline exposure. Median response duration was 5.6 months, time to progression was 4.5 months, and overall survival was 16.1 months. Although the most common grade 3 to 4 toxicities were hematologic, few neutropenic complications resulted. The most frequent nonhematologic toxicities were nausea and vomiting, fatigue, stomatitis, and hand-foot syndrome. One patient previously treated with an anthracycline developed a transient decrease (21%) in the left ventricular ejection fraction, with cardiac function recovering within 2 months. Conclusion: Pegylated liposomal doxorubicin in combination with gemcitabine is active and well tolerated in patients with metastatic breast cancer. Median overall survival was 16.1 months, and approximately 78% of patients derived clinical benefit from treatment. This regimen represents a therapeutic option for patients receiving front-line therapy for their metastatic breast cancer.

Tolerability of 2-Weekly CHOP+Rituximab Followed by Yttrium-90 Ibritumomab Tiuxetan (Zevalin) In Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL): Final Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4918-4918 ◽  
Author(s):  
Andrew Manson ◽  
Reem Karmali ◽  
Irene Dehghan-Paz ◽  
Eduardo Braun ◽  
Teresa O'Brien ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
Left Ventricular ◽  
Neutropenic Fever ◽  
Left Ventricular Ejection ◽  
Organizing Pneumonia ◽  
Off Label ◽  
Grade 3 ◽  
Dose Dense

Abstract Abstract 4918 Background: Improved outcomes have been demonstrated in DLBCL with dose dense CHOP (CHOP-14), the addition of immunotherapy to CHOP, and radioimmunotherapy consolidation following CHOP chemotherapy. A prospective, single-arm, open-label, nonrandomized phase II trial was conducted using a combination of the above with dose dense CHOP+R, every 2 weeks, followed by radioimmunotherapy consolidation to evaluate its efficacy and safety in untreated DLBCL patients. Patients and Methods: 20 eligible patients (measurable disease, age >18 years, performance status 0–2, adequate marrow, liver and kidney function) with previously untreated DLBCL were enrolled. Patients with transformed lymphoma were excluded. Patients received standard CHOP along with rituximab 375mg/m2 IV on day 1, every two weeks for 6 cycles, followed by Zevalin 6–8 weeks later. Efficacy of Study: In 20 treated patients, ORR was 100% with 90% CR and 10% PR. 16 patients received the entire treatment regimen as intended. 3 patients (15%) relapsed. All relapses were retreated with one patient now in CR and 2 deceased. One other patient, who did not receive Zevalin, is also deceased from organizing pneumonia 2 years after last chemotherapy. Safety Results: The most common adverse effects of this regimen were hematological. All patients (n=20) had anemia during CHOP+R pre-Zevalin, 15 (75%) patients with grade 1/2 and 5 (25%) with grade 3 anemia. 11 patients had thrombocytopenia, 4 with grade 3/4 toxicity. Neutropenia was present during CHOP+R therapy in 14 patients (70%), 2 cases of grade 2 and 12 cases of grade 4 toxicity. However, neutropenic fever only occurred in 4 patients, all with grade 1/2 neutropenia. Neuropathy was also a common toxicity (15 patients), with grade 3 toxicity occurring in 4 patients. Less common adverse effects, all ≤ grade 2, included anorexia, constipation, nephrolithiasis, diarrhea, urinary frequency, dysgeusia and rhinitis. With completion of dose dense chemotherapy, one patient had organizing pneumonia, one had grade 2 pneumonitis, and one had bronchiectasis, all precluding the use of Zevalin. Pre and post chemotherapy MUGA scans demonstrated stable left ventricular ejection fractions in all but one patient, who remains in CR. Zevalin was completed by 16 patients (80%). Zevalin induced grade 3/4 cytopenias occurred in 8 patients (50%), the most common being neutropenia (all 8 patients) with no cases of neutropenic fever. 12 (75%) patients experienced thrombocytopenia, though only 2 had grade 3/4 effects. Grade 3 syncope occurred in one patient. All other non-hematologic effects were ≤ grade 2 and included neuropathy, sinus and yeast infections, folliculitis, rash, diarrhea, nausea, and urinary incontinence. Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy is well tolerated, safe and non-life threatening among our sample population of untreated DLBCL. Disclosures: Off Label Use: Chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. We are administering R-CHOP every 14 days for dose intensification followed by zevalin (radioimmunotherapy) consolidation for untreated DLBCL. This regimen is off-label. Gregory: Amgen: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; Glaxo-Smith-Kline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx (Proteolix): Research Funding; Spectrum Pharmaceuticals: Consultancy.

Phase II study of pegylated liposomal doxorubicin plus vinorelbine in metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10718-10718 ◽  
Author(s):  
S. Del Prete ◽  
L. Montella ◽  
V. Faiola ◽  
R. Guarrasi ◽  
G. Busto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection

10718 Background: Pegylated liposomal doxorubicin and vinorelbine are active single agents in metastatic breast cancer (MBC) and lack overlapping toxicity. The possibility of combining these two drugs therefore seems attractive. Methods: Twenty-five patients with MBC entered a phase II study of pegylated liposomal doxorubicin 40 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 25 mg/m2 i.v. on day 1 and vinorelbine 60 mg/m2 oral on day 14, every 4 weeks. A two-staged Simon accrual design was adopted for this phase II trial. Patients were required to have measurable disease, previous chemotherapy with or without an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Results: Twenty-one patients with MBC were eligible, assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 36% (9 of 25; 95% CI, 20%-54%). One complete response and 8 partial responses were noted. In addition, 11 patients (44%) had stable disease of > 4 months duration, and 5 patients (20 %) had disease progression. Median time to disease progression was 10 months (range, 3–38 months) and median overall survival was 15 months (range, 4 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 30% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 8%) and mucositis (14%). Late alopecia was seen in 51% of patients (grade 1 in 39%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Only one patient presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and this patient recovered normal values after cessation of therapy. Conclusions: The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population. Final data analysis will be presented. No significant financial relationships to disclose.

Reduced Dose of Non-Pegylated Liposomal Doxorrubicin with Cyclophosphamide, Vincristine and Prednisone ± Rituximab for Elderly Patients with Aggressive Lymphoma Non Candidates to Standard Chemotherapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4464-4464
Author(s):  
Eva Gimeno ◽  
Alberto Alvarez ◽  
Carme Pedro ◽  
Eugenia Abella ◽  
Miquel Gomez ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Low Dose ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Aggressive Lymphoma ◽  
Left Ventricular Ejection ◽  
Standard Chemotherapy ◽  
Number Of Cycles

Abstract BACKGROUND: CHOP± Rituximab regimen is the standard regimen for elderly patients with aggressive lymphoma. However, many of these patients present formal contraindication for this type of treatment due to severe associated comorbidities. The aim of the study is to retrospectively evaluate the safety and clinical profile of a modified CHOP (with low dose non-pegylated liposomal doxorrubicin) ± Rituximab in elderly patients with clinically aggressive lymphoma which are not tributary to standard chemotherapy. PATIENTS AND METHODS. Retrospective analysis of 15 consecutively patients (pts) with previously untreated aggressive lymphoma. Gender: 9 men/6 women; median age: 76 years (62–85y). 6 pts had stage I–II (IPI=1–2) and 9 pts stage IV (IPI=2–5). Median baseline left ventricular ejection fraction (LVEF) was 60.2% (31–80%). Comorbidities: active chronic liver disease (1 pt), severe chronic obstructive pulmonary disease (3 pts), severe cardiomiopathy (4 pts) and others (7 pts). Schedule: non pegylated liposomal doxorubicin 30 mg/m2, cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg/d d1-5 ± rituximab 375mg/m2 d1) every 21 days, as a first line therapy. Pegfilgrastim was used on day 2 at standard dose. RESULTS. Nine pts are evaluable for efficacy at the time of this report (2 pts died early due to infectious complications and are not evaluable for response). Median number of cycles was 4 (range 4–6). Total number of cycles administered was 43. A complete response (CR) was achieved in 8 pts (88.8%) and partial response in 1 pt (11.1%) after chemotherapy. CR was achieved in this last patient after involved field radiotherapy. Two pts have relapsed during follow-up, all dying with active disease. OS at 12 months: 70% (CI95%: 42–98%) and PFS at 12 months: 60% (CI95%: 30–90%), with a median time of follow-up for surviving pts of 18 months (4–35 m). Treatment was well tolerated with grade III–IV neutropenia was 39.5% with 14% episodes of febrile neutropenia. No other relevant toxicities were observed. Of note, median LVEF was not significantly different between before and after treatment with one patient showing a clinical significant improve in his LVEF. CONCLUSION. This preliminary data indicate that low dose non-pegylated liposomal doxorubicin in modified CHOP regimen was active and well tolerated in patients with formal contraindications to standard therapy due to severe comorbidities. Further exploration of this regimen administered every 14 days is warranted.

Integration of Rituximab and Liposomal Doxorubicin (DOXIL®) Into CODOX-M/IVAC for HIV-Negative and HIV+ Adults with Untreated Burkitt's Lymphoma (BL): Results of a Prospective Multicenter Phase II Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2669-2669
Author(s):  
Andrew M. Evens ◽  
Kenneth R. Carson ◽  
Chadi Nabhan ◽  
Borko Jovanovic ◽  
Paul Barr ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Research Funding ◽  
Liposomal Doxorubicin ◽  
Cell Lymphoma ◽  
Survival Rates ◽  
B Cell Lymphoma ◽  
Burkitt’S Lymphoma ◽  
Grade 3 ◽  
Hiv Negative

Abstract Abstract 2669 Background: The survival of adult BL has improved with intensification of multi-agent chemotherapy, although 2-year survival rates remain <65–70%. Efforts to improve survival, as well as decrease treatment-related toxicities are needed. Further, there are no prospective clinical studies to date that have examined the addition of rituximab into the CODOX-M/IVAC regimen. Methods: Eligible patients for this investigator-initiated, 5-site phase II clinical trial included: newly diagnosed BL and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and BL (according to WHO 2008 definition) regardless of HIV status. Eligibility for HIV+ patients included: no evidence of multi-drug resistant HIV infection or concurrent AIDS defining illness and CD4 count >350/mcL. Patients were classified as low risk (LR) if they had all of the following factors present: 1) normal LDH, 2) stage I/II disease, 3) ECOG performance status (PS) <2, and 4) no mass >10 cm. All other patients were “high risk” (HR). LR patients received 3 consecutive cycles of CODOX-M, while HR patients received 4 alternating cycles of CODOX-M and IVAC. For CODOX-M, methotrexate 3.0 gram/m2 i.v. was used. Further, liposomal doxorubicin (40 mg/m2) was utilized in lieu of doxorubicin (day 1 of all CODOX-M cycles), while intravenous rituximab (500 mg/m2) was added to days 0 and day 8 of each CODOX-M cycle and days 0 and 6 of IVAC cycles. In addition, as a corollary analysis, frequent assessment of ejection fraction (EF) was performed in all patients (baseline, s/p 2 cycles, and 4 weeks after completion of therapy). Results: Twenty-five patients (22 male and 3 female) enrolled from March 2007 through April 2011. The median age was 44 years (range, 23–70 years). Furthermore, 5 (20%) patients were >60 years. All patients had classical BL, while 1 patient had concomitant BCL-2 expression. There were 20 HR and 5 LR patients; 3 of the HR and 1 LR patient were HIV+, while the remaining patients were HIV-negative. Median PS at study entry was 1, while PS=2 in 6 (24%) patients. Further, 3 (15%) HR patients had + central nervous system disease (2 parenchymal, 1 leptomeningeal). Additionally, 7 (35%) HR patients had bulky disease >10 cm (2 (10%) with dominant mass >20cm), 8 (40%) of all patients had bone marrow involvement, and 15 (75%) had an elevated LDH. 24 of 25 patients were evaluable for toxicity and response/survival. Therapy was completed at a median of 13.5 weeks (range, 11–20) for HR patients and a median of 10 weeks for LR (range, 9–12). With respect to toxicity, myelosuppression was overall comparable (58% of patients experienced grade 4 thrombocytopenia with only 4% grade 4 anemia) to prior CODOX-M/IVAC data, while the incidence of mucositis also appeared similar to prior reports (38% grade 3, 13% grade 4). Other clinically relevant grade 3 toxicities included neutropenic fever (33%), transaminitis (33%), diarrhea (8%), elevated creatinine (8%), and seizure (4%). Notably, there was no grade 3 or 4 neuropathy. After 2 cycles of therapy, two grade 2 and two grade 3 cardiac events were noted (all depressed EF, no clinical evidence of congestive heart failure). The two grade 3 events occurred in a 70-year-old and 69-year-old man, both with HR disease, and the latter with history of myocardial infarction. Among all patients, the median change in EF at baseline vs study end was: −2% (range, −22% to +11%). In terms of outcomes, the response rate after 2 cycles of therapy was 100% with a 67% complete remission (CR) rate. At a median follow-up of 24 months, the 2-year PFS and OS rates for all patients were 86% and 86%, respectively (LR 2-year PFS and OS both 100%; and HR 2-year PFS and OS both 82%). Furthermore, the 2-year PFS and OS rates for HR, HIV-negative patients were 91% and 91%, respectively (see Figure 1), while the disease-specific survival (DSS) for this subgroup of patients was 100%. Of the 3 deaths on trial, 2 were due to progressive disease in HIV+ HR patients, while the 3rd was a 71 year-old HIV-negative HR subject who died in CR at 14 months from unknown causes. Conclusions: Altogether, the integration of rituximab and liposomal doxorubicin into CODOX-M/IVAC for adult BL was feasible and associated with similar tolerability compared with prior reports. Additionally, this regimen was associated with excellent survival rates, especially for HIV-negative BL. Disclosures: Evens: Ortho-Biotec: Research Funding. Off Label Use: Doxil in the treatment of Burkitt's lymphoma. Carson:Genentech: Speakers Bureau. Nabhan:Genentech: Research Funding, Speakers Bureau. Gregory:Genentech: Advisory Board. Gordon:Genentech: Consultancy, Speakers Bureau.

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