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.

Modified-CHOP with Reduced Dose of Non-Pegylated Liposomal Doxorubicin ± Rituximab in First Line Treatment for Elderly Patients with Aggressive Lymphoma Non Suitables for Standard Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4752-4752
Author(s):  
Eva Gimeno ◽  
Blanca Sánchez ◽  
Alberto Alvarez ◽  
Carme Pedro ◽  
Eugenia Abella ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Liposomal Doxorubicin ◽  
Conflicts Of Interest ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Aggressive Lymphoma ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Reduced Dose

Abstract Abstract 4752 BACKGROUND CHOP ± Rituximab ( R) is the standard regimen for elderly patients (pts) with aggressive lymphoma but many of them are not suitable for it due to severe associated comorbidities. The aim was to evaluate retrospectively the efficacy and safety of a modified-CHOP (with reduced dose non-pegylated liposomal doxorubicin (NPLD) ± R in elderly pts with clinically aggressive lymphoma not tributary to standard anthracycline-containing chemotherapy. PATIENTS AND METHODS Retrospective analysis of 30 pts (16M/14W). Median age 76 years (60-88). Stage III-IV: 19 pts (58%). IPI 3-5: 16 pts (49%). Median baseline left ventricular ejection fraction (LVEF): 63% (33-80). Median NT-proBNP determination: 1431 ng/L (60-9120), 14 patients had NT-proBNP>900. All patients had one or more severe comorbidities. Schedule: NPLD 30mg/m2 (d1), cyclophosphamide 750mg/m2 (d1), vincristine 1.4mg/m2 (d1), prednisone 100mg/d (d1-5) ± R 375mg/m2 (d1) + Pegfilgrastim (d2) every 21 days. RESULTS Median follow-up time was 18 months. Median number of cycles was 4 (range 1-6). Complete response (CR/uCR): 24 pts (73%), Partial response: 4 pts (12%). Two pts progressed during chemotherapy and 10 pts relapsed during follow-up (5 of them dying with active disease). Overall Survival (OS) at 12 and 24 months was 76% (95%CI 61-91) and 70% (95%CI 49-91), respectively. Progression-free survival (PFS) at 12 and 24 months was 65% (95%CI 49-81) and 55% (95%CI 32-78), respectively. A total of 154 cycles were administered. 52% of patients showed grade III-IV neutropenia and 33% of them required hospital admission for febrile neutropenia. LVEF neither NT-proBNP value was significantly different before and after treatment with one patient showing an important improvement in his LVEF. Multivariate analysis recognized NT-proBNP determination >900ng/L as the most negative important factor in OS and PFD. CONCLUSION Disclosures: No relevant conflicts of interest to declare.

Cardiac safety profile of pegylated liposomal doxorubicin reaching or exceeding lifetime cumulative doses of 550 mg/m2 in patients with recurrent ovarian and peritoneal cancer

2008 ◽  
Vol 18 (2) ◽  
pp. 223-227 ◽  
Author(s):  
Y. Yildirim ◽  
E. Gultekin ◽  
M. E. Avci ◽  
M. M. Inal ◽  
S. Yunus ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Safety ◽  
Ventricular Ejection Fraction ◽  
Peritoneal Cancer ◽  
Number Of Patients

The objective of this study is to evaluate the cardiac safety of pegylated liposomal doxorubicin (PLD) reaching or exceeding a cumulative dose of 550 mg/m2 in patients with recurrent ovarian and peritoneal cancer. A total of 14 patients (11 ovarian cancer, 3 primary peritoneal cancer) who received PLD in our center between February 2004 and October 2006 met inclusion criteria of the study. PLD was administered at doses of 30 mg/m2 together with carboplatin or 50 mg/m2 as a single agent every 3–6 weeks. Left ventricular ejection fraction (LVEF) estimations performed by M Mode ultrasound (General Electric Vivid-3, Milwaukee, Wisconsin) and clinical cardiac status were used to detect PLD-related cardiotoxicity. The median cumulative dose of PLD was 685.5 mg/m2 (range 552–1015 mg/m2) and the median number of PLD courses was 9.5 (range 7–17). One patient had also been previously treated with conventional doxorubicin. LVEF scans were obtained on 10 of the 14 patients at the beginning of the therapy and on all patients at the end of therapy. No clinical evidence (symptoms or physical findings) of cardiac dysfunction had been observed in these patients either during active treatment or follow-up period. Despite small number of patients and lack of control group, our study suggests that the cumulative doses in excess of 550 mg/m2 of PLD seem to not carry a significant risk of cardiomyopathy as judged by LVEF and clinical follow-up.

scholarly journals Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Miguel J. Gil-Gil ◽  
Meritxell Bellet ◽  
Milana Bergamino ◽  
Serafín Morales ◽  
Agustí Barnadas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Elderly Patients ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Triple Negative ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular Ejection ◽  
Cardiac Safety

BackgroundThe CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS).MethodsIn this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m2) plus cyclophosphamide (600 mg/m2) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed.ResultsBetween Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%).ConclusionAt 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity.Trial Registration NumberClinicalTrials.gov reference NCT00563953.

scholarly journals Pegylated Liposomal Doxorubicin Versus Epirubicin as Adjuvant Therapy for Stage I–III Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxian Hu ◽  
Kezhen Lv ◽  
Rongyue Teng ◽  
Jida Chen ◽  
Chenpu Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Stage I ◽  
Left Ventricular Ejection ◽  
P Values

Background: Conventional anthracyclines, like epirubicin, are cornerstone drugs for breast cancer treatment of all stages, but their cumulative toxicity could cause life-threatening side effects. Pegylated liposomal doxorubicin (PLD), an effective anti-breast cancer drug, has lower toxicity than conventional anthracyclines. This retrospective study compared the efficacy and toxicity profiles between PLD and epirubicin as adjuvant therapy for breast cancer.Patients and Methods: A total of 1,471 patients diagnosed with stage I–III breast cancer between 2000 and 2018 were included in this study, among which 661 were treated with PLD and 810 with epirubicin, with 45.9 months as the median follow-up time. Anti-breast cancer efficacy was assessed with overall survival (OS) and disease-free survival (DFS), while cardiac toxicity was assessed with left ventricular ejection fraction (LVEF) and electrocardiogram (ECG).Results: The Kaplan–Meier method and Cox proportional hazards model revealed that there was no statistical difference in OS or DFS between patients treated with PLD and epirubicin, regardless of cancer stages or molecular subtypes (all p-values > 0.05). In addition, patients had significantly better LEVF and ECG data after adjuvant therapy with PLD (both p-values < 0.05).Conclusion: Based on the large sample size and the long follow-up time of this study, we conclude that PLD has a similar anti-breast cancer efficacy as epirubicin while inducing lower level of cardiac toxicity in Han Chinese. This study suggests that PLD-based adjuvant chemotherapy could be a better option than epirubicin for breast cancer patients especially with existing cardiac disease.

Pegylated liposomal doxorubicin in combination with gemcitabine in elderly women with locally advanced or metastatic breast cancer: Safety and activity results of our clinical experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12005-e12005
Author(s):  
B. Adamo ◽  
T. Franchina ◽  
N. Denaro ◽  
C. Garipoli ◽  
G. Ferraro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Clinical Benefit ◽  
Liposomal Doxorubicin ◽  
Elderly Women ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Grade 3

e12005 Background: Elderly breast cancer patients have an increased risk of toxicity from chemotherapy, especially from anthracycline-based regimens. Pegylated liposomal doxorubicin (PLD) has shown a better tolerability profile also in combination with gemcitabine (GEM), as evidenced in several phase II trials. The aim of this study is to retrospectively evaluate the safety and activity of this combination in chemo-naïve or pre-treated elderly patients with advanced breast cancer. Methods: From January 2006 to March 2008, 39 patients (pts) with age ≥ 65 received, at our institution, PLD 25 mg/m2 (day 1, q21) and GEM 800 mg/m2 (days 1 and 8, q21). Median age was 72 (range, 65–79). ECOG PS was 0/1/2 in 14/23/2 pts, respectively. 12 pts (31%) were chemo-naïve, 20 (51%) received prior adjuvant anthracycline-based regimens, and 7 (18%) received other chemotherapies. PLD-GEM combination was administered as first line in 35 pts (90%). Median left ventricular ejection fraction (LVEF) at baseline was 61% (range, 50%-75%). 28 patients (72%) had metastatic disease: 10 in liver, 6 in lung, 2 in skin, and 10 in multiple sites. Estrogen receptor was positive in 32 pts (82%); HER-2+ in 5 pts; 7 pts were triple negative. Results: A total of 206 cycles were administered with a mean number of cycles per patient of 5.2 (range, 3–12). Grade 3–4 neutropenia occurred in 4 (10%) and 3 patients (8%), respectively; grade 3 anemia in two pts (5%). Non-hematological toxicity was mild, with 5 cases (13%) of grade 3 mucositis, and 2 cases (5%) of grade 2 palmar-plantar erythrodysesthesia syndrome. No modifications in LVEF or toxic deaths were documented. We observed 1 CR (2.5%) and 11 PR (28.2%). Eighteen (44%) patients experienced SD for 16 weeks and an overall clinical benefit of 76.8%. Conclusions: The combination of PLD and GEM has a favorable tolerability and a safety profile with an evident clinical benefit and should represent an interesting treatment option in elderly women with advanced breast cancer. No significant financial relationships to disclose.

Cardiac safety profile of patients receiving high cumulative doses of pegylated-liposomal doxorubicin (PLD): Use of left ventricular ejection fraction (EF).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14016-e14016
Author(s):  
Keith M. Skubitz ◽  
Anne Hudson Blaes ◽  
Suma Konety ◽  
Gary S. Francis
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cumulative Dose ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Retrospective Chart Review ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Bolus Administration ◽  
Ventricular Ejection Fraction

e14016 Background: The use of doxorubicin (D) is limited by cardiotoxicity. Cumulative dose is an important risk factor for D-induced heart failure (D-HF). Retrospective studies found a ~7.5% incidence of clinical HF at a cumulative dose of 550 mg/m2, and prospective trials have found even higher rates. The administration of D by continuous intravenous infusion (CIVI) has less cardiotoxicity than when given by bolus administration. Pegylated-liposomal doxorubicin (PLD) has a longer half-life in blood, and may have lower cardiotoxicity. Limiting D use based on ejection fraction (EF) is commonly performed. Despite the wide use of EF to monitor D-HF, evidence for its utility to predict D-HF is limited, and monitoring adds cost. There is even less information regarding large cumulative doses of PLD and its effect on D-HF and EF. We examined the incidence of D-HF in patients who received a large cumulative dose of D as PLD, and its relation to EF and HF. Methods: A retrospective chart review of patients who received a large cumulative dose of PLD, sometimes following previous free D, was performed. Results: Definite clinical D-HF was not observed in 53 patients who received a cumulative D dose (free + PLD) of > 450 mg/m2, 46 of whom received > 500 mg/m2, 26 > 700 mg/m2, 14 > 1000 mg/m2, and 5 > 1400 mg/m2. The EF varied greatly over time in some patients in the absence of symptoms or signs of HF and was not a reliable predictor of the development of heart failure. Conclusions: The findings provide further evidence for the low risk of D-HF with PLD. Although this study is subject to the usual limits of a retrospective study, the doses received and long-term follow-up are noteworthy. While the determination of EF is commonly used to monitor D cardiotoxicity, it has many limitations. Serial monitoring of EF during treatment may not be helpful, at least in the case of PLD and CIVI-D in adults. Indeed, given the lack of prognostic clarity regarding modest EF changes, regular measurement of EF may sometimes inappropriately limit patient access to this useful drug. These findings may not apply to children or other liposomal formulations, such as non-pegylated formulations.

scholarly journals Histological evidence for the cardiac safety of high-dose pegylated liposomal doxorubicin in a patient with HIV-associated Kaposi sarcoma: a case report and literature review

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ayaka Ishihara ◽  
Shuji Hatakeyama ◽  
Jun Suzuki ◽  
Yusuke Amano ◽  
Teppei Sasahara ◽  
...  
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Cumulative Dose ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Pegylated Liposomal Doxorubicin ◽  
Kaposi Sarcoma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Background Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear. Case presentation A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient’s left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2. Conclusions This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.

Phase I trial of pegylated liposomal doxorubicin and lapatinib in the treatment of metastatic breast cancer (MBC): Final results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 610-610
Author(s):  
Mary E. Cianfrocca ◽  
Virginia G. Kaklamani ◽  
Steven T. Rosen ◽  
Jamie H. Von Roenn ◽  
Alfred Rademaker ◽  
...  
Keyword(s):  
Phase I ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Primary Objective ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Grade 3

610 Background: Liposomal formulations including pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index of anthracyclines (A). Lapatinib (L) is a selective, highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. Conventional doxorubicin plus trastuzumab was effective but with unacceptable cardiac toxicity. PLD plus L may be effective with less cardiac risk. Methods: This is a phase I, dose-escalation trial of PLD 20, 30, 45 and 60 mg/m2 IV every 4 weeks (maximum of 8 doses) and L, 1500 mg po daily until progression in patients (pts) with MBC. ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed. A subsequent amendment allowed prior L. Prior A use was limited to 240 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of > 50% was required. The primary objective was to evaluate the safety (particularly cardiac), tolerability and feasibility of PLD and L. Results: 23 pts (PLD: 20 mg/m2 - 4 pts; 30 mg/m2 - 3 pts; 45 mg/m2 – 13 pts; 60 mg/m2- 3 pts) have been treated; total of 73 treatment cycles. Dose-limiting toxicity (DLT) was not reached. One pt had an LVEF drop to < 50% after 4 cycles accompanied by a pericardial effusion due to progressive disease. Treatment-related grade III/IV adverse events included: 4 pts with hand-foot-syndrome (HFS), 2 pts each with leukopenia, infection, and skin changes, 1 pt each with pain, fatigue, diarrhea, mucositis, hypoalbuminemia, anemia, cough, pleural effusion, and edema. Grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Response data in 21 evaluable pts: 4 PR, 5 SD, and 12 PD. Preliminary pharmacokinetic (PK) analyses (7 pts) indicate L has no effect on PLD (45 mg/m2) concentrations, but L concentrations were approximately 2-fold higher the day of PLD dosing. Conclusions: In 23 pts treated, PLD plus L was well tolerated with manageable toxicities and no treatment-related cardiac toxicity. DLT was not reached however grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Preliminary PK analyses demonstrate no effect of L on PLD, but an effect of PLD on L the day of PLD dosing.

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.

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