Regimen In Elderly Patients Research Articles

A phase II study of chlorambucil plus rituximab followed by maintenance versus observation in elderly patients with previously untreated chronic lymphocytic leukemia: Results of the induction phase.

6629 Background: The FCR regimen (fludarabine, cyclophosphamide, rituximab) significantly improves the outcome of patients (pts) with chronic lymphocytic leukemia (CLL). However, myelotoxicity and immunosuppression are a limitation to the use of this regimen in elderly patients and in those with co-morbidities. The combination of rituximab (R) with chlorambucil (CLB; R-CLB) is an attractive therapeutic option for this subset of patients considering the expected good tolerability and potentially increased activity of this schedule. This study was designed to determine whether the R-CLB combination is a feasible and beneficial first-line treatment for elderly patients with CLL and to define the role of maintenance with R. Methods: 97 elderly patients requiring first-line therapy received CLB (8 mg/m²/day p.o., d1-d7, courses 1-8) and R (375 mg/m², course 3 and 500 mg/m², courses 4-8) every 28 days. Responsive patients were subsequently randomized to receive R maintenance (375 mg/m² every 2 months for 2 years) or clinical observation. The primary endpoint was the overall response rate after the R-CLB induction phase. Results: The median age of pts was 70.0 years (range: 61-84;≥70: 52.9%) and 47.1% showed ≥1 comorbidities. Binet’s B-C stage was observed in 74.1% of cases, 58% were IgVH unmutated, 24.1% showed adverse cytogenetic abnormalities (11q23-: 19.3%; 17p13-: 4.8%) and 4.8% a p53 mutation. Response was assessed on an ITT basis (at least 1 course of R-CLB) in 85 pts. The ORR was 81.2%, the CR rate, confirmed by CT scan, 16.5%, the CRi 2.4%, the nPR 2.4%, the PR 60% and the treatment failures 18.8% (PD:3.5%; SD:4.7%; early treatment withdrawn, 10.6%). No evidence of residual disease by 4-color flow cytometry in both PB and BM was detected in 2/14 CR patients. The most common hematologic toxicity was neutropenia (grade III-IV: 13.5% of pts). The median number of administered R-CLB cycles in patients <80 years was 6. Conclusions: The results of this study indicate that R-CLB is an active and well tolerated front-line regimen for elderly patients with CLL.

Gemcitabine plus carboplatin used as induction regimen for elderly patients with locally advanced unresectable non-small cell lung cancer

Objective The purpose of this study was to evaluate the efficacy and safety of gemcitabine (GEM) and carboplatin (CBP) used as induction regimen in the treatment of elderly patients with locally advanced unresectable non-small cell lung cancer (NSCLC).

Retrospective Analysis of the Experience with Rituximab and Methylprednisone In Elderly Patients with CLL

AbstractAbstract 4636 Background:Single agent rituximab has limited activity in chronic lymphocytic at standard doses; however, the addition of rituximab to purine analogues, monoclonal antibodies or steroids has been shown to improve responses and response duration in patients with untreated and relapsed chronic lymphocytic leukemia (CLL). The combination of rituximab and high dose methylprednisone has shown activity in patients with untreated and fludarabine-refractory CLL (Castro 2008, Castro 2009); however, there is limited reported experience with this regimen in elderly patients. These data prompted us to review our center's experience with rituximab in combination with high dose methylprednisone in elderly patients with CLL. Patients and Methods:We retrospectively identified 24 patients 65 years or older with CLL who received rituximab and methylprednisone between July 2002 and April 2010 at MD Anderson Cancer Center. Six patients received this treatment as initial therapy and 18 patients as salvage treatment. Rituximab 375–750 mg/m2 and methylprednisone 500–2000 mg were administered i.v. weekly for 4 weeks. Three patients received further maintenance treatment with rituximab 375–750 mg/m2 and methylprednisone 500 mg/m2 every month or every 3 months until failure of response. Responses were assessed according to 2008 NCI-WG criteria. Estimated progression free survival and OS were analyzed from time of treatment to progression or death using Kaplan-Meier survival curves. Results:The median age was 71 (65 – 87) years and 17 of 24 (71%) had Rai stage III or IV disease. Two patients had concomitant autoimmune hemolytic anemia (AIHA), one patient had immune thrombocytopenic purpura and AIHA was the indication for therapy in one patient. Median β2-microglobulin was 7.7 (2.3 – 21) mg/l and 5 patients had chromosome 17 abnormalities. Previously treated patients had received a median of 3 (1 – 7) prior treatments and 6 (32%) pts were refractory to fludarabine. Responses were observed in 4 of 6 untreated patients (ORR 67%) and included 3 clinical complete responses unconfirmed by bone marrow biopsy (CRu, 50%) and 1 partial response. The estimated median PFS and OS in this group were 13 and 55 months, respectively. Among patients who received rituximab and methylprednisone as salvage therapy, 7 patients achieved a partial response (ORR 39%), 10 (50%) patients failed treatment, 1 patient (6%) received another therapy after 1 cycle for lack of response and 1 patient (6%) was lost to follow-up. In the salvage group, estimated median PFS and OS were 4 and 18 months, respectively. Four deaths occurred 3, 5, 11 and 12 months after rituximab and methylprednisone without further therapy; 3 patients had progressive CLL and the cause of death was unknown in 1 patient. Grade 3 or 4 neutropenia, anemia and thrombocytopenia occurred in 6 (33%), 3 (14%) and 1 (5%) of evaluable patients. Four patients (17%) experienced grade 3 or 4 infections (3 pneumonia and 1 colonic abscess), 5 patients experienced minor infections and 3 patients experienced viral reactivations (1 CMV, 1 HSV, 2 VZV). There were four grade 3 or 4 non-hematological adverse events including grade 4 gastrointestinal and pulmonary hemorrhage (1), colitis (1), steroid myopathy (1) and peripheral edema (1). All grade 3 or 4 complication occurred in salvage patients. Conclusions:Based on our experience, rituximab and methylprednisone therapy can be safely administered to older patients with CLL. As previously reported by Castro et al, higher response rates were seen in untreated patients, whereas responses were less frequent and shorter lasting in patients with relapsed disease, although this group had high risk disease based on β2-microglobulin levels. Additional studies are required to explore the benefit of this regimen in elderly patients with CLL. Disclosures:Off Label Use: Ofatumumab and lenalidomide in patients with relapsed chronic lymphocytic leukemia. O'Brien:Celgene: Consultancy; Genentech BioOncology: Consultancy. Wierda:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech BioOncology: Advisory Board, Consultancy, Speakers Bureau. Estrov:Celgene: Consultancy. Keating:Celgene: Consultancy; Genentech: Consultancy. Ferrajoli:Celgene: Research Funding; Genentech: Research Funding.

5-Azacytidine as Salvage Treatment in Relapsed Myeloid Tumors after Allogeneic Bone Marrow Transplantation

Relapse after allogeneic blood or marrow transplantation carries a very poor prognosis. Current strategies for management that include donor lymphocyte infusions (DLIs) and salvage chemotherapies are usually toxic and ineffective. Here we report the outcome of 10 patients with myeloid malignancies that received 5-azacytidine after a failed allogeneic bone marrow transplant. Of the 10 patients, 6 achieved a complete remission, 1 had stable disease, and 3 progressed after a median of 6 cycles administered. Only 1 patient has died (of disease progression), and no flares of graft-versus-host disease (GVHD) were observed with 5-azacytidine. As of latest follow-up, the median overall survival (OS) for the group was 422.5 days (127-1411). These results further suggest that 5-azacytidine is an active agent after failing an allogeneic bone marrow transplant, and prospective studies are warranted.

Comparison of Allogeneic Hematopoietic Cell Transplantation and Chemotherapy in Elderly Patients with Non-M3 Acute Myelogenous Leukemia in First Complete Remission

The benefits of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with acute myelogenous leukemia (AML) in first complete remission (CR1) have mostly been evaluated in younger patients. Although favorable outcomes of allo-HCT over chemotherapy have been reported with the use of reduced-intensity conditioning (RIC) regimens in elderly patients with AML in CR1, information is still limited, especially on the effects of cytogenetic risks and donor sources. We collected data from AML patients aged 50 to 70 years who achieved CR1, and compared the outcome in 152 patients who underwent allo-HCT in CR1 (HCT group) to that in 884 patients who were treated with chemotherapy (CTx group). The cumulative incidence of relapse in the HCT group was significantly lower than that in the CTx group (22% versus 62%). Both overall survival (OS) and relapse-free survival (RFS) were significantly improved in the HCT group (OS: 62% versus 51%, P = .012), not only in the whole population, but also in the intermediate-risk group. Among patients who had a suitable related donor, the outcomes in the HCT group were significantly better than those in the CTx group. The introduction of appropriate treatment strategies that include allo-HCT may improve the outcome in elderly patients with AML in CR1.

Nutritional assessment with body mass index in elderly cancer patients: Influence of chemotherapy exposure.

e19614 Background: Nutritional aspects remain an important problem in elderly cancer patients care and cure. However, the real impact of chemotherapies regimens in elderly patients is not clearly established. The aims of the present study were to evaluate the nutritional status in a series of elderly cancer patients treated by common chemotherapies regimens. Methods: From May 2005 to October 2009, 375 patients aged over 70 years with solid malignancies were systematically treated by common chemotherapies regimens and registered in a prospective databank at the salpetriere hospital, in Paris. Body Mass Index (BMI) measurements were assessed at baseline and before each chemotherapy. According to Body Mass Index patients were classified as underweight (< 18.5), normal weight (between 18.5–24.9), overweight (25–29.9) and obesity (over 30). Results: One hundred sixty five male and 210 female with a mean age of 76.3 years (range 70-101.3) were evaluated. Each patient received between 1 to 16 lines of chemotherapy (median of 2) for a total of 1135 lines. More than 75 % of patients had a colorectal, breast, lung, ovary and prostate cancer. At baseline, 16 out of 375 elderly patients (4.2 %) presented a BMI under 18.5 and were considered as under weighted. At the end of the treatment 17 out of 375 patients (4.5 %) with a BMI under 18.5 and were considered as under weighted, 8 out 16 patients had an improvement in the initial BMI score and were at the end of evaluation well nourished and at the contrary 9 out 17 patients had a decrease of their initial BMI status Conclusions: Chemotherapeutic drugs and regimens did not influence the nutritional status as measured by BMI in this representative elderly patients treated by common chemotherapeutic regimens. No significant financial relationships to disclose.

Randomized phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer

BackgroundThe optimal platinum doublet regimen in elderly patients with non-small-cell lung cancer (NSCLC) is still uncertain. We conducted a randomized phase II study to compare the efficacy and safety of weekly paclitaxel combined with carboplatin with those of the standard schedule. Patients and methodsElderly patients (age ≥70 years) with advanced NSCLC were randomly assigned to either the weekly arm {70 mg/m2 paclitaxel on days 1, 8, and 15 and carboplatin [area under the curve (AUC)=6] on day 1} or the standard arm [200 mg/m2 paclitaxel and carboplatin (AUC=6) on day 1]. The primary end point was the overall response rate (ORR). ResultsEighty-two patients were enrolled. The ORR and median progression-free survival were 55% and 6.0 months for the weekly arm and 53% and 5.6 months for the standard arm. Grade 3/4 neutropenia and peripheral neuropathy were observed in 41% and 0% of the patients in the weekly arm and in 88% and 25% in the standard arm, respectively. ConclusionsThis is the first randomized study that compares the platinum doublet designed specifically for the elderly. Regarding the safety, the weekly regimen was less toxic than the standard regimen and seems to be preferable for elderly patients with advanced NSCLC.

Phase I/II trial of gemcitabine plus oral TS-1 in elderly patients with advanced non-small cell lung cancer: Thoracic oncology research group study 0502

A phase I/II trial of TS-1 combined with gemcitabine was designed to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients older than 70 years of age received TS-1 orally b.i.d. on days 1–14 and gemcitabine intravenously on days 8 and 15 every 4 weeks. In phase I ( n = 22), each cohort received escalating doses of TS-1 (30–40 mg/m 2 b.i.d.) and gemcitabine (800–1000 mg/m 2); MTD was 40 mg/m 2 b.i.d. TS-1 and 1000 mg/m 2 gemcitabine; RD was 30 mg/m 2 b.i.d. TS-1 and 1000 mg/m 2 gemcitabine. Dose-limiting toxicities included a grade 3 infection, skin toxicity, and stomatitis. In phase II ( n = 37), the overall response rate was 27% (90% confidence interval (CI): 15–42%) and the median time to progression and overall survival were 4.2 months (90% CI: 3.2–5.7) and 12.9 months (90% CI: 10.4–14.7), respectively. The most common grade 3 or higher toxicity was neutropenia (45.9%), and thrombocytopenia was observed in 13.5% of patients. Two cases each of grade 3 pneumonitis and skin toxicity were observed, but nonhematological toxicities occurred at generally low frequencies. TS-1 with gemcitabine is a promising doublet regimen in elderly patients with advanced NSCLC with acceptable toxicities.

Evaluation of various gentamicin dosage regimens in geriatric patients: a simulation study

The aim of this simulation study was to evaluate the ability of three regimens proposed in official French recommendations for gentamicin to hit defined pharmacokinetic (PK) and pharmacodynamic targets in a population of elderly patients. The first drug regimen tested consisted of a loading dose of 1 mg/kg and a maintenance dose weighted by creatininemia, every 8 h. The second regimen consisted of a fixed dose of 1 mg/kg at various intervals of time, calculated from creatinine clearance. The last regimen was a fixed dose of 3 mg/kg once a day. All regimens were for 5 days. We used a bicompartmental PK model and implemented a Monte Carlo simulation to generate a large sample of geriatric subjects. The analysis examined three ranges of creatinine clearance. Simulations showed that for the two regimens using multiple doses per day, neither was able to reach an efficacy level without significant toxicity after 5 days of treatment, regardless of the level of renal function. The use of creatininemia or creatinine clearance to adjust the drug dose did not alter these findings. The once-a-day dosing regimen gave better results both in efficacy and toxicity, except for patients with creatinine clearance lower than 60 mL/min, where the incidence of potential toxicity was above 25%. These results strongly suggest that official French recommendations about aminoglycoside dosage regimens in elderly patients with renal impairment should be updated, and that the frequent need for therapeutic drug monitoring and dosage individualization should be clearly stated.

Azacitidine Prolongs Overall Survival Compared With Conventional Care Regimens in Elderly Patients With Low Bone Marrow Blast Count Acute Myeloid Leukemia

In a phase III randomized trial, azacitidine significantly prolonged overall survival (OS) compared with conventional care regimens (CCRs) in patients with intermediate-2- and high-risk myelodysplastic syndromes. Approximately one third of these patients were classified as having acute myeloid leukemia (AML) under current WHO criteria. This analysis compared the effects of azacitidine versus CCR on OS in this subgroup. Patients were randomly assigned to receive subcutaneous azacitidine 75 mg/m(2)/d or CCR (best supportive care [BSC] only, low-dose cytarabine (LDAC), or intensive chemotherapy [IC]). Of the 113 elderly patients (median age, 70 years) randomly assigned to receive azacitidine (n = 55) or CCR (n = 58; 47% BSC, 34% LDAC, 19% IC), 86% were considered unfit for IC. At a median follow-up of 20.1 months, median OS for azacitidine-treated patients was 24.5 months compared with 16.0 months for CCR-treated patients (hazard ratio = 0.47; 95% CI, 0.28 to 0.79; P = .005), and 2-year OS rates were 50% and 16%, respectively (P = .001). Two-year OS rates were higher with azacitidine versus CCR in patients considered unfit for IC (P = .0003). Azacitidine was associated with fewer total days in hospital (P < .0001) than CCR. In older adult patients with low marrow blast count (20% to 30%) WHO-defined AML, azacitidine significantly prolongs OS and significantly improves several patient morbidity measures compared with CCR.

MPT Vs ThaDD in Very Elderly Patients with Multiple Myeloma: a Case-Match Study.

Abstract 1835Poster Board I-861Five studies demonstrated the superiority of MPT over MP regimen in elderly patients with MM not eligible for transplantation. In particular, one of these studies, showed this figure in patients aged more than 75 years who represent more than one third of MM patients. Nevertheless, in this latter study 42.5% of patients withdrawn from the MPT protocol because of toxicity. Therefore, there is a wide room of improving these results in this troublesome patient population. Using ThaDD regimen, including liposomal pegylated doxorubicin, we reported low haematological and non-hematological toxicity in elderly and

Cyclophosphamide, Vincristine, Myocet and Prednisone ± Rituximab (COMP±R) Regimen Is Safe and Effective as First Line or Salvage Therapy in Elderly Non Hodgkin Lymphoma (NHL): Preliminary Data of Single Centre Experience.

Abstract 3747Poster Board III-683 Backgrounddespite the prognosis of aggressive non-Hodgkin Lymphoma has considerably improved over the past decades, the treatment of elderly patients with NHL is still a difficult challenge for the clinician.A retrospective EORTC study conducted in patients with aggressive NHL and age above 70 years showed that about half of patients received an aggressive treatment and that only 15% of investigators employed full-dose regimens from the first cycle.We here present the preliminary data of CHOP-like regimen delivered as first-line or salvage therapy to elderly or young patients with NHL and not eligible for more aggressive therapy. Patients and methodsfrom July 2006 to January 2009, 27 pts (M/F:11/16) with a median age of 71 years (range: 53-84) were included in the study.Twenty-four pts (88%) were more than 65 yo, 18 (66%) had high-grade and 9 (34%) an indolent lymphoma. Stage III-IV disease according to Ann Arbor staging occurred in 18 pts (66%) whereas aaIPI, evaluated only for pts with aggressive NHL, was 3 2 in 9 pts (18%). ENS involvement ≥ 1 was present in 11 (41%) and BM involvement in 13 pts (48%). Most of pts (60%) had ECOG PS ≥ 1. Twenty out of 27 pts (74%) received COMP±R as first-line treatment and 7 (26%) as salvage therapy; all but one of pre-treated pts had received more than 1 line of chemotherapy (range 2-4). Twenty-five (92%) pts had co-morbidity with more than 1 disease in 44% of cases. Median LVEF was 59% (range: 35-80%). COMP±R regimen consisted of cyclophosphamide 750 mg/m2 IV d1, vincristine 1.4 mg/m2 IV d1 (capped at 2mg), liposome-encapsulated doxorubicin (MyocetÒ) at the dose of 50 mg/m2 IV d1 and Prednisone 100 mg/die PO d 1-5 with or without Rituximab at dose of 375 mg/m2 d8 at first course and at d1 of subsequent courses according to B or T-cell lymphoma phenotype respectively. To pts with early stage disease were planned 4 courses of COMP±R±IF-RT while those with advanced stage of disease received six courses of chemotherapy delivered every 3 weeks. Median number of cycles delivered was 5.6 (range: 4-8). All patients completed the planned treatment and most of them (92%) received G-CSF at dose of 300 mg/die as primary (67%) or secondary (25%) prophylaxis. ESA support was need in 8 pts (30%). Resultscomplete response (CR) was achieved in 21 (78%) and partial response (PR) in 3 (11%) of pts with an ORR of 89%; three pts had stable (n=2) or progressive disease (n=1). The regimen was safe and well tolerated with dose reduction occurring in 9 pts (34%). None of pts developed cardiac toxicity. The mainly adverse events recorded was neutropenia occurring in 15% of pts and febrile neutropenia in 6 pts (23%). Extra-haematological toxicity was mild (WHO grade 1-2) and recorded in 18% of pts. There was no treatment-related fatal toxicity. With a median follow-up of 15 months (range 6-33) the OS and EFS was 93% and 89% respectively. ConclusionCOMP±R regimen shows to be safe and effective in a group of elderly patients both as first line or salvage therapy. However more patients and longer follow-up is required to assess definitively the role of this regimen in elderly patients with untreated aggressive NHL. A prospective phase II trial is ongoing at our Institution.Tab. 1Response According to HistologyDLBCL (n=12)MZL (n=6)MCL (n=3)PTCL (n=3)FL (n=2)B-CLL (n=1)CR (%)11 (90)4 (66)2 (66)2 (66)2 (100)0PR (%)01 (16)1 (34)1 (34)00ORR %90%821001001000Tab. 2Response According to Status at TreatmentFirst line (n=20)Relapsed (n=7)CR (%)16 (80)5 (71)PR (%)3 (15)0ORR %9571 Disclosures:No relevant conflicts of interest to declare.

Comparing safety and efficacy of first‐line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer

Irinotecan-based chemotherapy regimens are 1 option for treatment of metastatic colorectal cancer (mCRC). The authors report the safety and efficacy of such regimens in elderly patients using a large phase III trial (bolus, infusional, or capecitabine with camptostar-celecoxib [BICC-C]) cohort. In period 1, 430 previously untreated patients with mCRC were randomized in a 3-by-2 design to receive irinotecan plus infusional 5-fluorouracil, and leucovorin (FOLFIRI), irinotecan plus bolus 5-fluorouracil/leucovorin (mIFL), and irinotecan plus oral capecitabine (CapeIRI). In period 2, an additional 117 patients were randomized to receive FOLFIRI or mIFL and bevacizumab. In both periods patients were also randomized to a double-blind treatment with celecoxib or placebo. A secondary analysis was conducted examining the safety and efficacy of these regimens in elderly (age >70 years) versus nonelderly (age <or=70 years) patients. In period 1, 19.5% of patients were elderly, compared with 24.8% in period 2. Rates of grade 3 and higher toxicity did not differ significantly between age groups in either period by treatment arm, with the exception of asthenia in the FOLFIRI and CapeIRI arms (P = .05 and P = .03, respectively) and dehydration in the CapeIRI arm in period 1 (P = .02). Overall progression-free survival for FOLFIRI in both periods was not statistically different by age. Objective responses and overall survival did not differ by patient age within treatment arms and periods. Irinotecan/fluoropyrimidine combinations are well tolerated in the elderly population, with similar efficacy to that found in nonelderly patients in first-line mCRC.

A105 A Phase III Study of MEL200 Versus MEL100 in Newly Diagnosed Myeloma Young Patients

Introduction and Aims: New agents have been introduced as induction prior to autologous stem cell transplantation (ASCT) and as consolidation/maintenance thereafter to improve complete response (CR) rates. We evaluate bortezomib plus pegylatedlyposomal-doxorubicin and dexamethasone (PAD) as induction prior to reduced intensity ASCT, followed by consolidation with lenalidomide and prednisone (LP) and maintenance with lenalidomide alone (L). Materials and Methods: Newly diagnosed multiple myeloma patients aged 65-75 years were eligible. Induction consisted of four 21-day PAD cycles (bortezomib 1.3 mg/m2 days 1, 4, 8, 11; pegylated-lyposomal-doxorubicin 30 mg/m2 day 4; dexamethasone 40 mg days 1-4, 8-11, and 15-18). Patients were conditioned with tandem melphalan 100 mg/m2 (MEL100) followed by stem cell support. After ASCT patients received consolidation with four 28-day LP cycles (lenalidomide 25 mg days 1-21, prednisone 50 mg every other day) followed by lenalidomide maintenance (10 mg days 1-21). Primary objectives were safety (grade 3 nonhematologic toxicity 35%). Results: One-hundred and two patients entered the study. After PAD, 94% of patients achieved at least partial response (PR) and 59% at least very good partial response (VGPR) including 13% CR. After tandem MEL100, 88% of patients obtained at least VGPR and 41% CR. After LP all patients achieved PR, 88% at least VGPR including 53% CR. After a median follow-up of 14 months, 1-year progression-free survival (PFS) was 92%, and 1-year overall survival was 92%. PFS was not significantly affected by b2-microglobulin levels (P = .10), presence of chromosome 13 deletion (P = .5) or t(4;14)(P = .61). During PAD, grade 3/4 adverse events included thrombocytopenia (13%), neutropenia (11%), infections (18%), gastrointestinal toxicities (12%), peripheral neuropathy (11%) and deep vein thrombosis (DVT) (6%). During LP, grade 3/4 toxicities included neutropenia (18%), thrombocytopenia (6%), infections (6%) and DVT (6%). The other grade 3/4 toxicities occurred in less than 5% of patients. Conclusion: Bortezomib as induction, followed by lenalidomide as consolidation/maintenance is a highly effective regimen in elderly patients. Updated results will be presented at the meeting.

Multicenter Phase II Study of Pegylated Liposomal Doxorubicin in Combination with Vinorelbine as First-Line Treatment in Elderly Patients with Metastatic Breast Cancer

Background: This multicenter phase II trial was conducted to analyze the clinical activity and toxicity of the combination of pegylated liposomal doxorubicin and vinorelbine as first-line treatment in elderly patients with metastatic breast cancer. Patients and Methods: From August 2002 to August 2004, 42 patients with metastatic breast cancer were recruited for treatment with pegylated liposomal doxorubicin 40 mg/m² intravenously (i.v.) on day 1 and vinorelbine 30 mg/m² i.v. on days 1 and 15 every 4 weeks. Results: The median age of the patients in this trial was 68 years (range 60–82). 40% of patients had 2 or more sites of metastasis, 33 (78%) had predominantly visceral metastasis, and 7 (16%) mostly bone metastasis. Just 2 (5%) patients had only lymphogenous or soft tissue metastasis. All patients had an ECOG performance status of 0–1, but 70% of the patients had relevant comorbidities. In an intention-to-treat analysis, the overall clinical response rate was 36%, the complete response rate was 2%, and the rate of partial remissions was 34%; stable disease occurred in 30%, and progressive disease was observed in 36%. Median duration of response was 10 months. Median time to progression was 4 months, and median overall survival time was 24 months. Conclusion: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well tolerated regimen in elderly patients with metastatic breast cancer in first-line treatment.

Preliminary Results of a Multicenter Phase II Trial of 5-Day Decitabine as Front-Line Therapy for Elderly Patients with Acute Myeloid Leukemia (AML)

Introduction: More than half of patients diagnosed with AML are over 60 years old and have few effective treatment options due to both patient-related factors such as co-morbidities and poor performance status, and high-risk disease features such as complex cytogenetics and preceding myelodysplastic syndrome (MDS). Decitabine, a potent DNA hypomethylating agent, has been approved for the treatment of patients with all FAB subtypes of MDS, including those with secondary MDS and those who have received prior therapy for MDS. In AML, decitabine may target the frequent aberrant DNA methylation patterns and is a lower intensity therapy that may be better tolerated in this challenging patient population.Study: The primary objective of this multicenter, open label Phase II trial was establishing the morphologic complete response (CR) rate in patients 60 years and older with newly diagnosed, untreated AML, who were not candidates for standard induction chemotherapy. Decitabine was administered at a dose of 20 mg/m2 intravenously over 1-hour for 5 consecutive days every 4 weeks.Results: Fifty-five patients were enrolled in the trial [27 men, 28 women; median age: 74 years (range, 61–87); ECOG Score: 0 (47%), 1 (35%), or 2 (18%)]. Most patients had intermediate (53%) or poor (42%) risk cytogenetics. Fifty-six percent had de novo AML, 35% were transformed from MDS, 7% had AML secondary to prior therapy, and 2% had other. According to the AML response criteria (Cheson, JCO 2003), the expert-reviewed overall response rate in the intent-to-treat (ITT) population was 26%, with 13 (24%) morphologic complete responses (CR) and 1 (2%) CR with incomplete blood count recovery (CRi) (Table). The median time to response was 3 months (range, 51–164 days). Responses were seen in all subgroups of patients, including 5 of 19 patients with a prior history of MDS (CR or CRi, 26%) and 5 of 23 patients with poor-risk cytogenetics (22%). A median of 3 cycles (range, 1–25) was administered to the ITT population. Sixty-four percent of patients received 3 or more cycles of therapy. Twenty-four patients (44%) maintained stable disease during a median 5 cycles of therapy. With 1-year duration of follow-up, the overall median survival was 9.6 months. Besides myelosuppression, the most commonly reported adverse events considered possibly related to decitabine treatment were febrile neutropenia (24%), fatigue (24%), pneumonia (11%), sepsis (9%), dyspnea (9%), and bacteraemia (7%). Three deaths occurred on study and were attributed to sepsis. The 30-day mortality rate on this trial was 4%, which compares favorably to the ~20% mortality rate typically seen in this population treated with standard induction therapy (Stone RM. CA Cancer J Clin. 2002; 52(6):363).Conclusion: These preliminary results suggest that decitabine given daily for 5 days demonstrates efficacy in patients with newly diagnosed AML, with a toxicity profile that was manageable in this elderly patient population. This study supports the investigation of decitabine in an ongoing Phase III survival trial (n=480) of the 5-day regimen in elderly patients with AML.TableNCRCRiOverall Response Rate %All Patients5513126%AML DiagnosisDe novo317023%Transformation from MDS194126%Secondary to Prior Therapy42050%Other1000%Cytogenetic RiskPoor235022%Intermediate296124%

Bortezomib-Doxorubicin-Dexamethasone as Induction Prior to Reduced Intensity Autologous Transplantation Followed by Lenalidomide as Consolidation/Maintenance in Elderly Untreated Myeloma Patients

Background: New agents have been introduced as induction prior to autologous stem cell transplant (ASCT) and as consolidation/maintenance thereafter to improve complete response (CR) rates. In this trial we evaluate Bortezomib plus Pegylated-lyposomal-doxorubicin and Dexamethasone (PAD) as induction therapy prior to reduced intensity ASCT, followed by consolidation with Lenalidomide and Prednisone (LP) and maintenance with Lenalidomide alone (L).Methods: Newly diagnosed multiple myeloma (MM) patients aged 65–75 years were eligible. Induction regimen consisted of 4 21-day PAD cycles (Bortezomib 1.3 mg/m2 days 1, 4, 8, 11, Pegylated-lyposomal-doxorubicin 30 mg/m2 day 4 and Dexamethasone 40 mg days 1–4, 8–11, 15–18). Two cycles of Cyclophosphamide 3 g/m2 plus Granulocyte-Colony Stimulating Factor were used to harvest stem cells. Patients were conditioned with tandem Melphalan 100 mg/m2 (MEL100) followed by stem cell support. After ASCT patients received consolidation with 4 28-day LP cycles (Lenalidomide 25 mg days 1–21 plus, Prednisone 50 mg every other day) followed by Lenalidomide alone maintenance (10 mg days 1–21 every 28 day). Primary objectives were safety (grade 3 non-hematologic toxicity < 30%) and efficacy (near CR rate > 35%).Results: One-hundred and two patients have been enrolled. After PAD cycles at least partial response (PR) rate was 94%, at least very good partial response (VGPR) was 59% including 13% CR. After tandem MEL100, 88% of patients achieved at least VGPR and 41% CR. After LP consolidation all patients obtained PR, 88% at least VGPR and 53% immunofixation negative CR. After a median follow-up of 14 months, 1-year progression free survival (PFS) was 92%, 1 year time to progression was 97% and 1 year overall survival was 92%. PFS was not significantly affected β2-microglobulin levels (p=0.10), presence of chromosome 13 deletion (p=0.5) or t(4;14) (p=0.61).During PAD, grade 3–4 adverse events included thrombocitopenia (13%), neutropenia (11%), infections (18%), gastrointestinal toxicities (12%), peripheral neuropathy (11%) and deep vein thrombosis (6%). During LP consolidation, grade 3–4 toxicities included neutropenia (18%), thrombocytopenia (6%), infections (6%) and deep vein thrombosis (6%). The other grade 3–4 toxicities occurred in less than 5% of patients.Conclusions: Bortezomib as induction regimen prior to reduced intensity ASCT, followed by Lenalidomide as consolidation maintenance is a highly effective regimen in elderly patients. Updated results will be presented at the meeting.

Vergleich verschiedener Therapieschemata zur Behandlung von 1–2 Hirnmetastasen bei älteren Patienten

Elderly patients are often treated differently than younger individuals due to concerns regarding tolerance and survival. This analysis was performed to evaluate whether elderly patients with one to two brain metastases would benefit from relatively aggressive approaches. It compares whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), resection plus WBRT (OP + WBRT), and resection plus WBRT plus boost (OP + WBRT + boost) in elderly patients. One-hundred-and-sixty-four patients aged > or = 65 years with one to two brain metastases treated with WBRT (n = 34), SRS (n = 43), OP + WBRT (n = 41), or OP + WBRT + boost (n = 46) were included. The groups were compared retrospectively regarding survival (OS), intracerebral control (IC), and local control of treated metastases (LC). Six additional potential prognostic factors were evaluated: gender, performance status, tumor type, number of brain metastases, extracerebral metastases, and interval from tumor diagnosis to irradiation. 1-year OS was 17% after WBRT, 40% after SRS, 27% after OP + WBRT, and 61% after OP + WBRT + boost. On multivariate analysis, treatment regimen (RR: 1.67; p = 0.043), no extracerebral metastases (RR: 2.85; p < 0.001), and longer interval from tumor diagnosis to irradiation (RR: 1.78; p = 0.002) were associated with improved OS. 1-year IC was 17%, 55%, 36%, and 79%, respectively. On multivariate analysis, treatment (RR: 2.83; p < 0.001), single brain metastasis (RR: 1.80; p = 0.021), and longer interval (RR: 2.02; p = 0.004) were associated with improved IC. 1-year LC was 19%, 68%, 43%, and 84%, respectively. On multivariate analysis, treatment (RR: 3.31; p < 0.001), single brain metastasis (RR: 1.76; p = 0.047), and longer interval (RR: 1.89; p = 0.015) were associated with improved LC. OP + WBRT + boost appeared to provide the best outcomes of the compared treatment regimens in elderly patients with one to two brain metastases. If surgery is not possible, SRS may be considered.

Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia

Understanding the causes of failure in older patients with acute lymphocytic leukemia (ALL) may help improve treatment strategies for patients in this particular age group. The objectives of the current study were to define the causes of death in older patients (aged > or = 60 years) with ALL during induction and consolidation-maintenance with a dose-intensive regimen of alternating 8 courses of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) with high doses of methotrexate and cytarabine followed by maintenance with 6-mercaptopurine, vincristine, methotrexate, and prednisone and to compare their outcomes with the outcomes of older patients who received earlier, less intensive regimens and younger patients who received hyper-CVAD. One hundred twenty-two older patients who received hyper-CVAD were compared with 34 older patients who received less intensive regimens and with 409 younger patients who received hyper-CVAD. The complete response (CR) rates in older patients receiving hyper-CVAD, older patients receiving other regimens, and younger patients receiving hyper-CVAD were 84%, 59%, and 92%, respectively (P < .001); and the respective induction mortality rates were 10%, 12%, and 2% (P not significant in older patients). The incidence of disease resistance during induction was 5%, 27%, and 2%, respectively (P < .001). The majority of deaths were related to infections. Among patients who achieved a CR, death in CR was noted in 34%, 15%, and 7% of older patients receiving hyper-CVAD, older patients receiving other regimens, and younger patients, respectively (P < .001); and the respective rates of recurrence were 40%, 80%, and 48% (P = .004). The estimated 5-year survival rates were 20%, 9%, and 48%, respectively (P < .001). The results of the current study suggested that intensifying the chemotherapy in older patients with ALL reduced the incidence of leukemia resistance but increased the incidence of death in CR from myelosuppression-associated infections. The overall benefit:risk ratio was favorable. Identifying novel, low-intensity agents/regimens for older patients with ALL may improve the results further.

Impact on autonomy of biweekly docetaxel as first-line chemotherapy (CT) regimen in elderly patients with metastatic breast cancer (MBC) – A FNCLCC Gerico Group Phase II multicentre trial

Impact on autonomy of biweekly docetaxel as first-line chemotherapy (CT) regimen in elderly patients with metastatic breast cancer (MBC) – A FNCLCC Gerico Group Phase II multicentre trial