Efficiency and toxicity of mifamurtid in childhood osteosarcoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e22010-e22010 ◽  
Author(s):  
Nurdan Tacyildiz ◽  
Sonay incesoy Ozdemir ◽  
Emel Cabi Unal ◽  
Handan Dincaslan ◽  
Gulsan Yavuz ◽  
...  
Keyword(s):  
Back Pain ◽  
Side Effects ◽  
Progressive Disease ◽  
Liver Enzymes ◽  
Complete Surgical Resection ◽  
Severe Back Pain ◽  
Grade 3 ◽  
Few Data ◽  
Disease Location

e22010 Background: There are only few data concerning efficiency and toxicity of mifamurtide in children with osteosarcoma (OS). The aim of this study was to evaluate efficiency and side effects of mifamurtide in childhood OS. Methods: We retrospectively analyzed the data of 18 patients with OS and who received mifamurtide between January 2012 and December 2016. Four hundred seventy seven doses of 2 mg/m2intravenous mifamurtide, along with paracetamol premedication were given in 15 patients with primary non-metastatic OS after complete surgical resection and 3 patients with progressive OS. Results: There were 11 males and 7 females, and the median age was 14 years (ranged, 9-18). The median follow-up time was 20 months (ranged, 7-51). The metaphyseal plates around the knee was the most frequent disease location with 94.4%. The median necrosis percentage was 94 (range, 35-100). All patients received Euromos protocol. The most common side effects were chills and fever (17/18). These reactions were observed in 4 patients during every administration, in only one patient at last administration and in the remaining 12 patients during first or first two administration. Headache, myalgia and arthralgia were observed in 2 patients during every infusion. In another one case, headache was observed during only first two infusions and he also hearing loss was developed (could be related CisPlatin) Back pain was observed in two patient during first infusion but one them suffered with severe back pain after few doses and stoped Mifamurtid. . Grade 3-4 neutropenia, trombocytopenia, abnormal liver enzymes and abnormal BUN and creatinin levels were not observed in patients who received mifamurtide alone after completion of chemotherapy. Of the 15 patients with primary non-metastatic OS treated with the addition of mifamurtide to chemotherapy, 13 showed complet remission for median 24 months (ranged,16-36) and 2 patients are still under treatment with complet remission. Of the 3 patients with progressive disease, 2 died and 1 had progressive disease for 51 months. Conclusions: Mifamurtide therapy is safe and well tolerated in childhood OS. Chills and fever were the major side effects, These events were transient and often no longer observed in subsequent administrations.

Phase II trial with carboplatin/gemcitabine induction chemotherapy followed by radiotherapy concomitantly with paclitaxel/gemcitabine in stage III non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7139-7139 ◽  
Author(s):  
V. Hirsh ◽  
M. Duclos ◽  
L. Souhami ◽  
P. Del Vecchio ◽  
L. Ofiara ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Liver Enzymes ◽  
Phase Ii Trial ◽  
Stage Iii ◽  
Stage Iii Nsclc ◽  
Grade 3 ◽  
One Year ◽  
Ecog Ps

7139 Background: The optimal combination of concomitant thoracic radiotherapy (TRT) and CT in stage III unresectable NSCLC remains unclear. The role of induction CT with Cb/G regimen, less toxic than Cisplatin/G, has not been established in stage III NSCLC. Methods: Forty-two patients (pts), 41 evaluable, entered this trial between January 2003 and November 2004, 27 males, 14 females, median age 60 (37–70), 19 pts with ECOG PS 0, 22 pts with PS 1, 22 pts with stage III A (N2), and 19 pts with stage III B (N2, N3). They received Cb AUC 5 i.v. on day 1 and G 1000 mg/m2 i.v. on days 1 + 8 every three weeks x 2 cycles, followed on day 50 by TRT, 60 Gy over 6 weeks, concomitantly with P 50 mg/m2 i.v. and G 100 mg/m2 i.v. on days 1 + 8 every three weeks x 2 cycles. Results: After induction CT, partial response (PR) was 73.1% (30 pts), stable disease (SD) 24.4% (10 pts), and 2.5% (1 pt) had progressive disease. After TRT and P/G, 19.5% (8 pts) had CR, 75.6% (31 pts) PR, and 4.9% (2 pts) PD. Median time-to-disease progression was 11.5 months. Median survival has not been reached yet, but surpassed 16.5 months; one-year survival is 71% (29 pts). Twenty three patients are still alive, after minimal follow-up of 13 months. First site of PD was in lungs in 7 pts, in brain 5 pts, in bones 4 pts; 2 pts died without PD, of cardiovascular disease. Toxicity of induction CT was minimal. During TRT and CT, grade 3 neutropenia, thrombocytopenia, and anemia occurred in 8 pts, 3 pts, and 3 pts respectively, grade 4 neutropenia and thrombocytopenia in one pt each. Nine pts received red cell transfusions, one pt platelet transfusion. One patient developed esophageal fistula with grade 4 toxicity, 3 pts had grade 3 esophagitis, 2 pts grade 3 infections, and one pt grade 3 dermatitis and elevation of liver enzymes. Conclusions: This regimen is effective, well tolerated, and appears to be an excellent choice for stage III NSCLC. Sponsored by Eli Lilly Canada. [Table: see text]

scholarly journals A Phase 1/2 Trial of Pomalidomide, Dexamethasone and Pegylated Liposomal Doxorubicin for Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4774-4774
Author(s):  
James R. Berenson ◽  
Laura V. Stampleman ◽  
Alberto Bessudo ◽  
Peter J. Rosen ◽  
Leonard M Klein ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Liposomal Doxorubicin ◽  
Phase 1 ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Great Promise ◽  
Phase 2 ◽  
Grade 3

Abstract Background Immunomodulatory drugs (IMiD), such as thalidomide and lenalidomide (LEN) and its newest derivative pomalidomide (POM), have shown great promise for the treatment of multiple myeloma (MM) patients (pts). POM has in vitro anti-MM potency and has shown efficacy for the treatment of relapsed/refractory (RR) MM pts. POM with dexamethasone (DEX) induces responses even for MM pts who are refractory to bortezomib (BORT) and LEN (Richardson et al, 2012). Pegylated liposomal doxorubicin (PLD) with BORT is FDA-approved for the treatment of MM pts who have received one prior therapy not containing BORT. The combination of PLD and LEN or thalidomide has shown efficacy for both RR and frontline MM pts (Offidani et al, 2006; 2007). We have also demonstrated that both the efficacy and tolerability of LEN in combination with DEX, PLD and BORT (DVD-R) may be improved by changing the doses and schedules of these drugs (Berenson et al, 2012). Based on these results, we hypothesized that the combination of POM, DEX and PLD would be effective for the treatment of RRMM pts. Thus, we conducted the first study investigating the safety and efficacy of POM in combination with intravenous (IV) DEX and PLD as a phase 1/2 trial using a modified dose, schedule and longer 28-day cycles for pts with RRMM. Methods The phase 1 portion enrolled MM pts w/ progressive disease whereas those enrolled in phase 2 also had to be refractory to LEN (single-agent or in combination), as demonstrated by progressive disease while receiving their last LEN-containing regimen or relapsed within 8 weeks of their last dose of this IMiD. Pts who have previously received POM treatment were ineligible. In the phase 1 portion, POM was administered at 2, 3 or 4 mg daily in three cohorts on days 1-21 of a 28-day cycle and DEX (40 mg) and PLD (5 mg/m2) were fixed and given intravenously on days 1, 4, 8, and 11. Results As of June 20th, 2014, 48 pts were enrolled in the trial and a total of 47 pts had received study drug. Pts had received a median of 4 prior treatments (range 1-18), with a median of 2 prior IMiD-containing regimens (range, 0-8). Fifty-three percent of the pts had received a prior PLD-containing regimen and 21% had received a prior IMiD and PLD combination treatment. Among all enrolled pts, 40 pts discontinued treatment and seven remain active. Pts completed a median of 3 cycles (range: 1-8), with a median follow-up time of 5.4 months (range: 0-22). During the phase 1 portion of the trial, the maximum tolerated dose (MTD) of POM was established at 4 mg. Enrollment of pts into the phase 2 portion of the trial began at the MTD. However, neutropenia ≥ grade 3 was observed at this dose in 10/17 (58.8%) phase 2 pts; and, as a result, the protocol was amended so that the MTD was lowered to 3 mg for all pts subsequently enrolled. Among the 36 pts enrolled in phase 2, 78% percent were refractory to LEN and steroids with or without other agents and 47% had previously received PLD. A median of 2 cycles (range, 1 to 8) were administered among the pts enrolled in phase 2. Thirty-five pts were evaluable for response as one pt was active but had not yet had any post-baseline disease assessments. Among all pts enrolled in phase 2, the overall response rate (ORR) and clinical benefit rate (CBR) were 29% and 49%, respectively, with 6 pts (17%) showing stable disease and 12 pts (34%) demonstrating progressive disease. For all pts enrolled in phase 2, the median follow-up time was 4.7 months (range 0-12) and the median PFS was 5.3 months. ORR and CBR for pts in the phase 2 were higher among pts receiving POM at 3 mg (32% and 58%, respectively) than among pts receiving POM at 4 mg (25% and 37%, respectively). Pts receiving the 4 mg dose of POM experienced more toxicities resulting in discontinuations, which likely explains the lower ORR and CBR observed among pts receiving this POM dose. Common ≥ grade 3 adverse events observed throughout the trial were neutropenia (21 pts; 44.7%), lymphopenia (10 pts; 21.3%), and hyponatremia (4 pts; 8.5%). One pt died of grade 5 sepsis. Conclusions This phase 1/2 trial is the first evaluating POM with PLD and DEX and demonstrates that the combination of POM at 3 mg, PLD and DEX using a modified 28-day cycle schedule is safe and effective for the treatment of MM pts refractory to LEN. Disclosures Berenson: Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Swift:Celgene: Consultancy, Honoraria. Vescio:Celgene: Honoraria.

scholarly journals Long-Term Sustained Responses Following Ibrutinib Discontinuation after Frontline Therapy with Obinutuzumab Plus Ibrutinib in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Paula A. Lengerke Diaz ◽  
Michael Y. Choi ◽  
Eider F. Moreno Cortes ◽  
Jose V. Forero ◽  
Juliana Velez-Lujan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Combination Regimen ◽  
Grade 3

Single oral targeted therapies have emerged as a standard of care in chronic lymphocytic leukemia (CLL). However, accessibility, side effects, and financial burden associated with long term administration limit their clinical use. Mainly, it is unclear in what clinical situation discontinuation of oral therapy can be recommended. The combination of type II anti-CD20 antibody obinutuzumab-Gazyva® with ibrutinib (GI) has shown a significant progression-free survival benefit in patients (pts) with CLL, including those with high-risk genomic aberrations. We conducted a phase 1b/2, single-arm, open-label trial to evaluate the safety and efficacy of GI as first-line treatment in 32 CLL pts. We report the outcome in pts that discontinued ibrutinib (either after 3 years of sustained complete response (CR) as stipulated in the clinical protocol, or due to other reasons). CLL pts enrolled in this protocol were ≥65 years old, or unfit/unwilling to receive chemotherapy. Pts received GI for six cycles, followed by daily single-agent ibrutinib. The protocol was designed to ensure that pts with a sustained CR after 36 months were allowed to discontinue ibrutinib. The median age was 66 years (IQR 59-73), and 6% of the evaluated pts had 17p deletion. All pts were able to complete the six planned cycles of obinutuzumab. The combination regimen was well-tolerated, and the most common adverse events (>5% CTCAE grade 3-4) were neutropenia, thrombocytopenia, and hyperglycemia. The rate and severity of infusion-related reactions (IRR) were much lower than expected (Grade≥ 3, 3%), and pts without IRR had lower serum levels of cytokines/chemokines CCL3 (P=0.0460), IFN-γ (P=0.0457), and TNF-α (P=0.0032) after infusion. The overall response rate was 100%, with nine pts (28%) achieving a CR, and four pts (12.5%) with undetectable minimal residual disease (uMRD) in the bone marrow, defined as <10-4 CLL cells on multicolor flow cytometry. At a median follow-up of 35.5 months (IQR 24.5-42.7) after starting treatment, 91% of the enrolled pts remain in remission with a 100% overall survival. Sixteen pts have completed a long-term follow-up of 36 months. Six pts showed CR, with three of them achieving uMRD in the bone marrow. Ten of these pts were in PR, and only one had disease progression and started treatment for symptomatic stage I disease with obinutuzumab plus venetoclax. In total, thirteen pts (41%) have stopped ibrutinib, with a median time on treatment prior to discontinuation of 35 months. Five (16%) of these pts had CRs and discontinued after 36 months. Eight additional pts (25%) had PRs and discontinued ibrutinib without being eligible: three pts discontinued prior to 36 months due to toxicities, and five pts discontinued after 36 months (3 due to side effects, and 2 due to financially driven decision). One patient eligible to discontinue ibrutinib, decided to remain on treatment despite sustained CR. After a median follow up time following ibrutinib discontinuation of 8 months (IQR 3.5-17), only two out of 13 pts have progressed (10 and 17 months after Ibrutinib discontinuation). None of the pts that stopped ibrutinib after achieving a CR have shown signs of disease progression. Of note, the pharmaceutical sponsor provided ibrutinib for the first 36 months, after which pts or their insurer became financially responsible. This particular scenario could bias the discontinuation pattern compared to a real world experience. It also provided us with a perspective about diverse factors affecting the treatment choices of pts. In summary, the obinutuzumab plus ibrutinib combination therapy was well-tolerated, with a much lower IRR rate. Efficacy compares favorably with historical controls with all pts responding to therapy, no deaths associated with treatment or disease progression, and a longer than expected time-to-progression after discontinuation of ibrutinib. The rate of ibrutinib discontinuation was higher than reported in the literature, most likely influenced by the protocol design and financial decisions driven by the switch from sponsor-provided ibrutinib to insurance or self-paid medication. Our observations regarding safety, efficacy and lack of disease progression after ibrutinib discontinuation are encouraging, and warrant confirmation in long-term prospective studies. Clinicaltrials.gov Identifier NCT02315768. Funding: Pharmacyclics LLC. Disclosures Choi: AbbVie: Consultancy, Speakers Bureau. Amaya-Chanaga:AbbVie: Ended employment in the past 24 months, Other: Research performed while employed as an investigator of this study at UCSD.. Kipps:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Castro:Kite Pharma: Research Funding; Pharmacyclics: Research Funding; Fate Therapeutics: Research Funding.

Platelets Recovery and Transfusion Needs after Reduced Intensity Conditioning (RIC) Allogeneic Peripheral Blood Stem Cell (PBSC) Transplantation (allo-SCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2989-2989
Author(s):  
Thomas Prebet ◽  
Mohamad Mohty ◽  
Patrick Ladaique ◽  
Christian Chabannon ◽  
Catherine Faucher ◽  
...  
Keyword(s):  
Platelet Count ◽  
Acute Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Platelet Recovery ◽  
Gvhd Prophylaxis ◽  
Study Population ◽  
Grade 3 ◽  
Few Data

Abstract Few data are currently available regarding platelets trasfusion needs and the kinetics and predicitive factors for platelets recovery after RIC allo-SCT. In this study, we analyzed the profile of platelets recovery and transfusion needs in the first 100 days after sibling PBSC RIC in a single institution series of 166 consecutive transplantations. Patients and graft characteristics were: age 49 y. (range: 18–70), diagnoses: 66 myeloid malignancies (40%), 64 lymphoid malignancies (39%), and 36 metastatic solid tumors (21%). 112 pts (67%) received an ATG-based RIC, while 54 pts (33%) received a low dose irradiation-based RIC. 75 pts (45%) developed grade 2–4 acute GVHD. Platelets recovery (>20 G/L) was observed at a median of 9 days (range: 0–99). The kinetics profile of platelets recovery is shown in the figure below. In the whole study population, the nadir was observed around day +7 after allo-SCT, and a plateau was reached about day +35. Filtered and irradiated donor apheresis platelets were used and patients needed a median of 1 unit (range: 0–53). In this series, 83 pts (50%) did not require any platelets transfusion during the follow-up period (median follow-up: 442 days) and 83 patients (50%) received at least one transfusion of platelets (54 were not transfused beyond day +100 after allo-SCT). Platelets count prior to RIC allo-SCT (median count 144 G/L; HR 0.44 (0.28–0.7) p=0.002), conditioning regimen (use of ATG; HR 1.86 (1.08–3.2) p=0.025) and the occurrence of acute (HR 1.54 (1.17–2.01); p=0.001) and severe GVHD (HR 2.36 (1.38–3.05) p=0.0006; 82% of patients with grade 3–4 acute GVHD were transfused) were the parameters significantly associated with platelets transfusion needs in multivariate analysis. In this cohort, 145 pts could be assessed for platelets recovery at day +100: among them, 99 (68%) had a platelet count >99 G/L. Univariate analysis found a significant impact of acute GVHD (p=0.0001) and platelet count prior to conditioning (p=0.012) but only acute GVHD (HR 5.52 (2.48–12.25); p=0.001) was associated with a delayed platelet recovery in a multivariate model. No impacts of pathology, GVHD prophylaxis regimen or CD34+ cell dose were demonstrated. Overall, these observations show a significantly lower rate of platelets transfusions and a quicker kinetic of platelets recovery after RIC allo-SCT and point out the effect of acute GVHD. In addition, considering the low level of myeloablation observed, RIC could be an appropriated field of investigation for the testing of megakaryocytic stimulating agents, towards further improving the safety and outcome of RIC allo-SCT. Platelets recovery after PBSC RIC allo-SCT Platelets recovery after PBSC RIC allo-SCT

Fludarabine and Mitoxantrone for the Refractory Relapse Treatment of B-Cell Low-Grade Non-Hodgkin Lymphoma (NHL): LACOHG First Interim Report (Latin American Cooperative Oncology Hematology Group).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4665-4665
Author(s):  
Severiano Baltazar-Arellano ◽  
Patricia Pimentel ◽  
Luis Vera ◽  
Fernando Bezares ◽  
Jose Málaga ◽  
...  
Keyword(s):  
B Cell ◽  
Latin American ◽  
Progressive Disease ◽  
Performance Status ◽  
Previous Treatment ◽  
Low Grade ◽  
Ecog Performance Status ◽  
Ann Arbor ◽  
Grade 3

Abstract Background: fludarabine (F) is licensed for the management of indolent non Hodgkin’s lymphoma in countries such as Canada and Switzerland. Clinical evidence suggests that fludarabine monotherapy is as least as effective, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL achieving objective response rates. Better response rates can be achieved combining F with Mitoxantrone (M) in low grade NHL even in refractory relapsed (RR) patients (pts). The Latin American Cooperative Oncology Hematology Group (LACOHG) proposed a multicenter study in Latin American countries in 2002 to use FM in RR B-cell low grade NHL. Aims: to assess the response rate, safety, disease free survival (DFS) and overall survival (OS) of FM in RR B-cell low grade NHL during (2003–2006). Methods: Forty-eight patients in the period of January 2003 to February 2006 were evaluated. Forty-four pts. had follicular lymphoma and 4 small lymphocytic lymphoma. Median age 63.5 years old (range: 24–83). Gender: female 56% and male 44%. Inclusion criteria for low grade NHL-LG was: any previous treatment excluding autologous transplantation, Ann Arbor stage II to IV, age > 18 years old, ECOG performance status 0–2 and written informed consent. ECOG performance status 0: 2%, 1: 71% and 2: 27%. Ann Arbor staging: II: 2%, III: 29% and IV: 69%. International Prognostic Index (IPI): 0–1: 19%, 2–3: 71% and 4–5: 10%. Median previous treatment was 1 (range: 1–3). FM treatment consisted of F 25 mg/m2 i.v. (day 1–3) and M 10 mg/m m2 i.v. (day 1) each 28 days for 6–8 cycles. Results: on this low grade NHL cohort the overall response rate (ORR was 81%; progressive disease and non-response 19%. With a median follow up of 17 months, OS at 24 months was 86% (DE 5.2%) and DFS at 24 months 57.1% (DE 11.3%). LDH in serum was not an adverse prognostic factor for DFS and OS. Safety: on the 286 cycles in 48 pts, the toxicity was: 18 episodes of grade 3-4 neutropenias, 15 episodes of grade 3-4 thrombocytopenia, 7 episodes of grade 1–2 nausea/vomiting, grade 1–2 diarrhea in 4 pts, 8 pts were admitted to the clinic, 11 fever episodes, 2 allopecia, 4 pts developed grade 1–2 peripheral neuropathy and infections 7%: one case herpes zoster. Mortality rate: 12,5% (6/48 patients), 5 of them because progressive disease. No cardiac toxicity was reported. Conclusions: FM is an effective and safe treatment for RR low grade NHL. A longer follow up and a larger trial, might be needed to confirm these results in a multicenter, randomized study. DFS with FM in RR low grade NHL : LACOHG DFS with FM in RR low grade NHL : LACOHG

Outcome of Patients Age 60 and Over with Acute Lymphoblastic Leukemia (ALL) Treated with a Modified Pediatric Protocol

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3962-3962 ◽  
Author(s):  
Susan Kao ◽  
Wei Xu ◽  
Vikas Gupta ◽  
Mark Minden ◽  
Andre Schuh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Side Effects ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Induction Phase ◽  
Cns Prophylaxis ◽  
Grade 3 ◽  
One Year ◽  
The One

Abstract Acute lymphoblastic leukemia (ALL) in patients over age 60 years is a poor prognosis disease with complete remission rate of 50–60% and median overall survival of less than a year. Between July 2004 and June 2007, we treated 17 elderly patients with newly diagnosed ALL with a modified pediatric protocol that included a remission induction phase, a CNS prophylaxis phase with intrathecal chemotherapy × 4, a 21-week intensification phase (7 cycles × 3 weeks each), and a 72-week maintenance phase. Induction chemotherapy consisted of vincristine 2 mg weekly × 3, doxorubicin 30mg/m2 × 2 doses, methotrexate 40mg/m2 × 1, asparaginase 12,000/m2 U × 1, and dexamethasone 40mg/day × 8 doses; BCR-ABL+ patients received imatinib mesylate 400 mg daily × 16 days instead of asparaginase. The intensification phase consisted of vincristine 2 mg × 7 doses, doxorubicin 30mg/m2 × 7 doses, asparaginase 6000 U/m2 weekly × 21 doses, 6-mercaptopurine 14/21 days, and dexamethasone 6 mg BID × 5/21 days. BCR-ABL+ patients received imatinib 400 mg daily × 14/21 days instead of asparaginase. Maintenance was the same as intensification except that no asparaginase was given. The median age was 66 years (range 60–78 years). Seven patients (41%) were BCR-ABL+ and four (24%) were pre-B with WBC > 30. Major side effects during the induction phase included infection (71%), hyperglycemia requiring insulin (24%), and cardiac toxicity (18%). The complete remission (CR) rate was 71% with an induction mortality of 29%. Of the five induction deaths, four were due to bacterial sepsis or pneumonia, and one was due to tumor lysis syndrome. CNS prophylaxis was well-tolerated except in one patient who required IV hydration for nausea/vomiting. Eleven patients proceeded to intensification. Major side effects during the intensification phase included infections (64%), peripheral neuropathy (64%), thrombosis (27%), and grade 3 nausea/vomiting (27%). Two patients required hospitalization during the intensification phase; there was one myocardial infarction and one acute pancreatitis. Eleven patients proceeded to the maintenance phase; major side effects during maintenance included infections (36%) and grade 3 peripheral neuropathy (18%). Two patients (17%) have relapsed, both during early maintenance phase; both had had a number of dose modifications and delays during intensification. The one year overall survival (OS) was 71% and the median OS has not been reached. After a median follow-up duration of 17 months (range 9–40 months), the median relapse-free survival (RFS) of the CR patients has not been reached; the one year RFS was 82%. These results show that administering a modified pediatric protocol to patients over age 60 years with ALL is feasible with an improved CR rate than generally reported. The OS and RFS also compare favorably to previously reported results, although further follow-up is required. However, induction mortality was high, and infectious complications persisted throughout the entire course of induction and intensification, though much diminished during the maintenance phase. Accrual to the protocol is continuing.

Demographics, Treatment Patterns, Safety, and Real-World Effectiveness in Patients ≥70 Years of Age with Chronic Lymphocytic Leukemia Receiving Bendamustine with or without Rituximab,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3914-3914
Author(s):  
Kathryn S. Kolibaba ◽  
Avani D. Joshi ◽  
James A. Sterchele ◽  
Michael Forsyth ◽  
Erin Alwon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
Partial Response ◽  
Real World ◽  
Progressive Disease ◽  
Lymphocytic Leukemia ◽  
Social Security Administration ◽  
Grade 3

Abstract Abstract 3914 Background Bendamustine is a unique, well-established alkylating agent with multifaceted actions leading to cancer cell death in several hematologic malignancies. In a phase 3 trial in treatment-naïve patients with chronic lymphocytic leukemia (CLL), rates of response and progression-free survival (PFS) were significantly superior to those for chlorambucil [Knauf WU et al. J Clin Oncol 2009;27:4378–84]. In vitro studies have found that the cytotoxic activity of bendamustine against CLL-derived cell lines is synergized by rituximab, an anti-CD20 monoclonal antibody [Demidem A et al. Cancer Biother Radiopharm 1997;12:177–86]. Older patients may demonstrate lower tolerance to chemoimmunotherapy [Foon KA & Hallek MJ. Leukemia 2010;24:500–11], and published clinical data on bendamustine-rituximab in CLL are scarce. Thus, this retrospective study sought to characterize a population of adults ≥70 years old with CLL receiving bendamustine with or without rituximab, describe patterns of care, assess data on real-world effectiveness outside of the controlled environment of clinical trials [Waldthaler C et al. Wien Klin Wochenschr 2011;123:269–275], and assess safety. Methods Records were extracted from US Oncology iKnowMed (iKM) record databases for all outpatients ≥70 years old with CLL (but no other tumor) and more than 1 visit recorded (but not enrolled in clinical trials) who received bendamustine between March 2008 and May 2010. Patients were classified as treatment-naïve or relapsed (including ≥ second-line therapy). To ascertain mortality, the iKM data were supplemented with vital-status data from the Social Security Administration Death Index. The overall response rate (ORR) included complete response (CR), nodal partial response (nPR), and partial response (PR). PFS was time from first bendamustine dose to progressive disease (change in line of therapy), relapse, or death from any cause. Data from patients who did not die, or had no progression and were lost to follow-up were censored. Results Among 91 patients, the mean (SD) initial age at beginning of first therapy was 77.4 (5.6) years, age at diagnosis was 70.3 (6.5) years, and 63.7% were male. Of the 16 (17.6%) treatment-naïve patients, 10 had received bendamustine monotherapy and 6 received bendamustine-rituximab. Of the 75 (82.4%) relapsed patients, 20 had received bendamustine monotherapy and 55 received bendamustine-rituximab. The observed ORR for treatment-naïve patients was 56.3% (n=9; 18.8% CR, 37.5% PR, and 0 nPR); 6.3% had progressive disease. For relapsed patients, the ORR was 58.7% (n=44; 13.3% CR, 44.0% PR, and 1.3% nPR); 24.0% had progressive disease. Among patients with data, median PFS for 16 treatment-naïve patients has not been reached (median follow-up 15.1 months); for 73 relapsed patients, PFS was 18.4 months. Kaplan-Meier estimates for PFS over time for each group are shown in the Figure. No unexpected toxicities were seen. The overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% for treatment-naïve patients and 25.3% for relapsed patients. Other grade 3/4 adverse events (AEs) included upper respiratory infection and abdominal pain in the relapsed group as well as rash and sepsis in both groups (n=1 each). The most frequent nonhematologic AEs (≥5%, any grade) were fatigue (33.0%), weight loss (11.0%), infection (9.9%; herpes zoster [n=2]; cryptococcal sepsis, Klebsiella sepsis, and pneumonia [n=1 each]), gastrointestinal (8.8%), fever (8.8%), pulmonary (6.6%), and rash (5.5%). o = data censored. Conclusions In this retrospective chart review of patients ≥70 years old with CLL, bendamustine, either alone or with rituximab, provided meaningful response rates and was generally well tolerated. The length of PFS of both treatment-naïve and relapsed patients was clinically meaningful. This research was sponsored by and conducted in collaboration with Cephalon, Inc., Frazer, PA. Disclosures: Sterchele: Cephalon, Inc.: Employment. Beygi:Cephalon, Inc.: Employment. Kennealey:Cephalon, Inc.: Employment.

Management of antiangiogenics’ renovascular safety in ovarian cancer subgroup and intermediate results of the MARS study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5067-5067
Author(s):  
Vincent Launay-Vacher ◽  
Nicolas Janus ◽  
Joseph Gligorov ◽  
Frédéric Selle ◽  
Francois Goldwasser ◽  
...  
Keyword(s):  
Renal Function ◽  
Side Effects ◽  
Clinical Setting ◽  
De Novo ◽  
Treatment Withdrawal ◽  
French Society ◽  
Anti Vegf ◽  
Vegf Pathway ◽  
Grade 3

5067 Background: Anti-VEGF drugs (AVD) are widely used in cancer patients (pts). Hypertension (HTN) and proteinuria (Pu) are class-side-effects of AVD, related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Methods: Hypertension (HTN) and proteinuria (Pu) are class-side-effects of anti-VEGF drugs (AVD), related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of these drugs in the clinical setting. Results: Among 77 OC pts been included, 38 completed the study to date (1-year follow-up (f/u)). Median age at inclusion (introduction of the AVD) was 62 years. Diabetes and HTN prevalences were 5.2% and 7.9%, respectively. Baseline renal assessment retrieved: Pu 13.2%, Hu 7.9%, mean aMDRD 80.9 ml/min/1.73m2 and 3 pts with aMDRD<60. The incidence of de novo Pu during f/u was 36.4% (Table). All pts with Pu at inclusion improved, except one. Among pts with de novo Pu, 58.3% afterwards improved/normalized. No Grade 3/4 Pu has been reported (at inclusion or during f/u) and no Hu. 17.1% developed HTN. In addition, a mean renal function decrease of -2.7 ml/min/1.73m2/year was observed and 4 pts had aMDRD<60 at the end of f/u. 36.4% had grade 1 SCr increase (median increase of 15.9%) No thrombotic micro-angiopathy (TMA) has been reported. Conclusions: The results of the MARS subgroup of OC pts shows that 1) TMA remains rare, 2) Pu develops in 36.4% of the pts, however with no Grade 3/4, 3) less than 20% developed HTN, and 4) renal function was not especially impaired. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM et Al. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]

scholarly journals Bortezomib Maintenance Therapy after Induction with R-CHOP, ARA-C and Autologous Stem Cell Transplantation in Newly Diagnosed MCL Patients, Results of a Multicenter Phase II HOVON Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 339-339 ◽  
Author(s):  
Jeanette K Doorduijn ◽  
Monique C. Minnema ◽  
Marie Jose Kersten ◽  
Pieternella J Lugtenburg ◽  
Martin R. Schipperus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Maintenance Therapy ◽  
Phase Ii ◽  
Research Funding ◽  
Progressive Disease ◽  
Induction Treatment ◽  
High Dose ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Introduction. The standard first-line treatment of young and fit mantle cell lymphoma (MCL) patients consists of a rituximab containing induction of CHOP and high dose ARA-C, followed by high dose consolidation and autologous stem cell transplant (ASCT). Thus far, almost all patients relapse after ASCT. Bortezomib is a proteasome inhibitor with activity in MCL. We investigated in a randomized phase II study whether there was any indication that maintenance therapy with bortezomib after ASCT could improve the outcome of treatment, measured as event free survival (EFS). Methods. Patients 18-65 years with newly diagnosed MCL were treated with 3 cycles of R-CHOP and 2 cycles of ARA-C (2 x 2 g/m2 iv d1-4) and rituximab (375 mg/m2, iv d11). Patients in PR or CR continued with ASCT after BEAM conditioning. Patients with a PR or CR after ASCT, with a neutrophil count > 0.5 x 109/l and platelets > 80 x 109/l were randomized between bortezomib and no further treatment. Bortezomib 1.3 mg/m2 iv was given once every two weeks, for 2 years, starting between 6 - 12 weeks after transplantation. Results . Between October 2007 and February 2012, 140 patients aged 34-66 years (median 57) were registered. Five patients were not eligible. The MIPI score was low, intermediate, high or unknown in 57%, 32%, 10% and 1% respectively. All eligible patients started induction treatment with R-CHOP. Two patients did not receive the first ARA-C cycle, because of progressive disease and physician decision. Hundred-fifteen patients (85%) received the BEAM and ASCT. Reasons to stop protocol treatment before ASCT were: progressive disease (PD) (n=6), inadequate stem cell harvest (n=3), excessive toxicity (n=3), other reasons (n=8). The response after ASCT was CR/CRu in 99 patients (86%), PR in 15 (13%), unknown in 1 (1%). Only 62 patients (45%), aged 34-65 years (median 56) were randomized between bortezomib maintenance and no further treatment. Two patients were randomized, but not eligible. Reasons for no randomization were: not eligible (n=30), patient refusal (n=14), excessive toxicity (n=2, and other reasons (n=7). In each treatment arm 30 patients were included. The patient characteristics were well balanced, except the MIPI score. In the no maintenance arm 21 patients (70%) had a low MIPI, compared to 15 patients (50%) in the bortezomib arm, and 6 (20%) versus 11 (37%) patients had an intermediate MIPI score. In both arms 3 patients (10%) had a high MIPI. Fifteen patients (50%) in the maintenance group continued bortezomib for 2 years. Reasons to stop earlier were excessive toxicity (n=6), PD/relapse (n=4), patients refusal (n=3) and other (n=2). The main adverse events during maintenance therapy were neurologic (CTC grade 2: 14%, grade 3: 4%), and infectious (grade 2: 11%, grade 3: 7%). Three patients developed a secondary malignancy: a basal cell carcinoma in the no maintenance group, a melanoma and a prostate carcinoma in the bortezomib group. With a median follow-up of the patients still alive of 50.9 months EFS at 4 years for all patients is 61%, and the overall survival (OS) 78%. The median follow-up of the randomized patients still alive is 42.9 months. The EFS at 4 years is 72% without maintenance versus 71% in the patients randomized for bortezomib maintenance. The OS at 4 years also shows no significant difference between the groups, 90% versus 93% respectively. Conclusion. There is no indication that bortezomib iv maintenance in a frequency of once every 2 weeks does improve the EFS of newly diagnosed MCL patients after intensive induction treatment with R-CHOP, double ARA-C and BEAM followed by ASCT. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Doorduijn: Celgene: Consultancy; Janssen: Consultancy; Roche: Consultancy. Off Label Use: bortezomib maintenance in MCL. Minnema:Celgene: Consultancy; Jansen Cilag: Consultancy; Amgen: Consultancy. Kersten:janssen: Honoraria, Research Funding; takeda millennium: Research Funding; roche: Honoraria, Research Funding. Lugtenburg:Mundipharma: Consultancy; Servier: Consultancy; Janssen-Cilag: Consultancy; Celgene: Consultancy; Roche: Consultancy. Schipperus:Novartis: Consultancy. Zijlstra:Celgene: Consultancy; Roche: Consultancy.

scholarly journals Barriers to applying for medical rehabilitation: a time-to-event analysis of employees with severe back pain in Germany

2022 ◽  
Author(s):  
Julia-Marie Zimmer ◽  
David Fauser ◽  
André Golla ◽  
Andreas Wienke ◽  
Nadine Schmitt ◽  
...  
Keyword(s):  
Back Pain ◽  
Cox Regression ◽  
Medical Rehabilitation ◽  
Event Analysis ◽  
Pension Insurance ◽  
Randomized Sampling ◽  
Severe Back Pain ◽  
Physician Support ◽  
Age Range

Objective: Longitudinal studies on barriers to applying for rehabilitation in Germany are lacking in light of the suspected underutilization of rehabilitation services. The aim of this study was to examine application behaviour in persons with disabling back pain and to identify relevant predictors for making an application. Design: A prospective cohort study with randomized sampling of insurants in the German Pension Insurance, using a questionnaire at baseline and follow-up with linked administrative data for 1.5 years. Subjects/patients: Employed persons (age range 45–59 years) with a high degree of limitations due to back pain and a self-reported risk of permanent work disability (not applied for disability pension, no medical rehabilitation within the last 4 years). Methods: Multivariable Cox regression was used to examine the influence of pre-selected variables on making an application in the follow-up period. Results: Of 690 persons, only 12% applied for rehabilitation. Predictors for making an application were: support from physicians (hazard ratio (HR)=2.24; 95% confidence interval (95% CI) 1.32–3.80), family, and friends (HR=1.67; 95% CI 1.02–2.73), more pain-related disability days (HR=1.02; 95% CI 1.01–1.03), and worse work ability (HR=0.86; 95% CI 0.75–0.97). An intention to apply at baseline mediated the effect of family and physician support on the application. Conclusion: The low number of applications for rehabilitation despite disabling back pain indicates access barriers to, and underuse of, medical rehabilitation.

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