A phase I/II study of docetaxel /S-1 with radiation for esophageal cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15061-15061
Author(s):  
T. Hirai ◽  
H. Matsumoto ◽  
Y. Hirabayashi ◽  
A. Urakami ◽  
K. Yamashita ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Adverse Events ◽  
Phase I ◽  
Cancer Patients ◽  
Response Rate ◽  
Combined Therapy ◽  
Treatment Schedule ◽  
Clinical Phase ◽  
Number Of Patients ◽  
Grade 3

15061 Background: The combined therapy of CDDP/5-FU with radiation is the standard therapy for esophageal cancer patients. However, this therapy is associated with a comparatively high incidence of gastrointestinal disorders resulting in therapy interruptions and long hospital stays. Herein, we propose a new regimen of Docetaxel / S-1 combined with radiation to improve the success rate and outcome. The clinical phase Istudy was conducted from May, 2004 until June, 2006. and we report on the results in this paper. Methods: Patients were given S-1 (60mg/m2/day) orally from days 1 to 14, and Docetaxel (20mg/m2 in level 1, 25mg/m2 in level 2, and 30 mg/m2 in level 3) intravenously on days 1 and 8. Patients received radiation in 2.0 Gy daily fractions from days 1 to 21, for a total of 30 Gy. Patients were given a seven-day rest after the first course, and then treated with the same regimen from days 28 to 49.P The phase I study was completed for 10 cases. Results: All patients completed the treatment schedule, with no treatment-related deaths and no grade 4 adverse events were observed. As for hematotoxicity, one case revealed leucopenia of grade 3 and neutropenia of grade 2. A non-hematotoxic adverse event (grade 3 anorexia) was observed in one patient. The response rate evaluated by RECIST was 66 % (CR in 2 cases, PR in 4 cases). We assumed that the recommended dosage of TXT and S-1 was 30mg/m2 and 60mg/m2, respectively, combined with a radiotherapy dose of 60Gy. Conclusions: This combination therapy may be superior to other treatments because of its lower rate of adverse events and higher response rates. We continue this study to Phase II in order to generate data on the response rate and adverse effect rate in a greater number of patients with esophageal cancer. No significant financial relationships to disclose.

PS02.125: NEOADJUVANT CHEMOTHERAPY PLUS SURGERY FOR NON-T4 CSTAGE II/III ESOPHAGEAL CANCER: A SINGLE INSTITUTION EXPERIENCE IN JAPAN

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 156-157
Author(s):  
Masahiko Ikebe ◽  
Mitsuhiko Ohta ◽  
Masahiko Sugiyama ◽  
Masaru Morita ◽  
Yasushi Toh
Keyword(s):  
Esophageal Cancer ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Standard Treatment ◽  
Conflicts Of Interest ◽  
Radical Surgery ◽  
Hospital Death ◽  
Number Of Patients ◽  
Grade 3

Abstract Background In Japan, following the results of JCOG 9907 trial, neoadjuvant chemotherapy (NAC) and radical surgery has been a standard treatment for Non-T4 cStage II/III esophageal cancer. Since 2009 we have also positioned NAC as standard treatment. We examined treatment outcomes and problems in our institute. Methods From 2009 to 2015, there were 64 patients with non-T4 stage II/III esophageal cancer treated with chemotherapy who are planned to undergo curative surgery. The standard NAC regimen consists of 2 courses of CDDP/5-FU (CF) therapy. As standard surgical procedure, subtotal esophagectomy, cervical anastomosis, three regional lymph node dissection were performed. Results The number of patients was 23/41 cases of cStage II/III respectively. 53 patients (88%) completed two courses of NAC. At the end of first course, NAC was terminated due to adverse events in 4 cases and due to the increasing tendency of tumors in 7 cases. NAC-induced adverse events of grade 3 or higher consists of myelosuppression in 27 cases (42%), appetite loss in 5 cases and so on. Surgery was performed in 61 cases (95%), of which R0 operation in 56 cases (88%), R1 operation in 3 cases and R2 operation in 2 cases. Three patients did not undergo surgery due to progressive disease. There were 7 cases (11%) of postoperative complications of Grade 3 or higher, but there was no in-hospital death. In the histological therapeutic effect, there were 5/41/7/4/3 cases for Grade 0/1a/1b/2/3, respectively. Three-year and five-year overall survival rate of all 64 patients were 68% and 47%. In 56 patients who underwent R0 surgery, they were 76% and 61% respectively. Conclusion From the viewpoint of adverse events and postoperative complications, NAC plus radical surgery for cStage II/III esophageal cancer could be performed safely. Considering that more than 60% of the patients belong to cStage III, this treatment strategy resulted in relatively favorable prognosis. Disclosure All authors have declared no conflicts of interest.

Increased incidence of adverse events after concomitant hepatic arterial infusion plus systemic chemotherapy and bevacizumab for colorectal cancer with liver metastasis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 591-591
Author(s):  
S. Sadahiro ◽  
T. Suzuki ◽  
Y. Maeda ◽  
A. Tanaka ◽  
K. Okada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Adverse Events ◽  
Phase I ◽  
Systemic Chemotherapy ◽  
Response Rate ◽  
Hepatic Arterial Infusion ◽  
Progression Free Survival ◽  
Arterial Infusion ◽  
Grade 3

591 Background: FOLFOX+bevacizumab (BEV) is the standard systemic chemotherapy for metastatic colorectal cancer (CRC). We investigated the combination of FOLFOX4 and hepatic arterial infusion (HAI) in patients who had isolated liver metastasis from CRC. We also compared efficacy and safety between this combination therapy and its concomitant use with BEV. Methods: Twenty-five patients entered a phase I/II trial of HAI (5-FU 250 mg/d, leucovorin 25 mg/d; d1-7, q2w) combined with FOLFOX4. Fourteen other patients with a similar background received HAI + FOLFOX4 combined with BEV and the two regimens were compared. Results: In the phase I/II study, the recommended doses for FOLFOX were as follows: L-OHP, 85 mg/m2; l-LV, 100 mg/m2; 5-FU (bolus), 400 mg/m2; and 5-FU (infusion), 600 mg/m2. Sixteen patients who received this regimen showed a response rate of 93.8% (2 CR and 13 PR), a median progression-free survival of 323 days, and a one-year survival rate of 93.7%. In the subsequent phase II trial of HAI + FOLFOX4 with BEV, 14 patients were enrolled and the response rate was 78.6% (2 CR and 9 PR). The outcome was inferior when BEV was used concomitantly. The median numbers of doses were 10 (range: 1-27) for FOLFOX4 and 9 (1-27) for HAI without BEV, whereas the corresponding numbers with BEV were 8 (1-12) and 2 (0-9), respectively. There was a marked decrease in the number of HAI procedures when BEV was used. Thrombosis occurred in 8 patients who received concomitant BEV, which was the most common reason for cessation of HAI. Other adverse events (≥Grade 3) were neutropenia (n=7; 43.8%) and thrombocytopenia (n=2; 12.5%) without BEV or neutropenia (n=7; 43.8%) and diarrhea (n=1; 7.1%) with BEV, and no marked difference was seen between the two regimens. Both regimens were well tolerated. Severe neuropathy was only observed in 1 patient (6.3%; Grade 3) who received concomitant BEV. Conclusions: In the present study, HAI + FOLFOX combined with BEV caused thrombosis and disturbance of wound healing, thereby increasing the incidence of complications and making it difficult to continue treatment. These findings suggest that BEV should not be administered with HAI therapy. No significant financial relationships to disclose.

scholarly journals Efficacy and Safety of Histone Deacetylase Inhibitors in Multiple Myeloma - a Systematic Review of Early Phase Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5629-5629
Author(s):  
Sharoon Samuel ◽  
Muhammad Junaid Tariq ◽  
Muhammad Usman ◽  
Amna Khalid ◽  
Muhammad Asad Fraz ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Phase I ◽  
Hdac Inhibitors ◽  
Complete Response ◽  
Number Of Patients ◽  
Grade 3 ◽  
Early Phase Clinical Trials

Abstract Introduction Recent studies in novel therapies have created opportunities for new treatment regimens to be used in the management of multiple myeloma. Histone deacetylase (HDAC) inhibitors lead to epigenetic manipulation of multiple myeloma (MM) cells by reducing resistance to pro-apoptotic signals. Panobinostat is an FDA approved HDAC inhibitor for multiple myeloma. The aim of this article is to study the safety, efficacy and dose limiting toxicities of HDAC inhibitors in the early phase clinical trials in multiple myeloma. Methods We performed a comprehensive literature search for phase I & I/II trials of HDAC inhibitors during last ten years using following databases: PubMed, Embase, AdisInsight, and Clinicaltrials.gov. Studies involving HDAC inhibitors in multiple myeloma other than panobinostat irrespective of the age, sex or specific eligibility criteria were included. Results Out of 2537 studies, we included 25 trials (23 phase I, 2 phase I/II) of HDAC inhibitors in this systematic review having a total of 518 patients. Of these, 471(90.9%) patients were evaluable for response. Vorinostat (Vor) is the most studied drug used in 13 trials (n=281). Two trials had Vor-only regimen and the remaining 11 had combination regimens mostly with lenalidomide and bortezomib. Vor, in combination with lenalidomide (R), bortezomib (V) and dexamethasone (d) has showed 100% overall response rate (ORR) in 30 newly diagnosed multiple myeloma (NDMM) patients, (Kaufmann et al., 2016), fifty two percent patients achieved very good partial response (VGPR) and 28% patients showed complete response (CR). Another study using Vor + R regimen after autologous stem cell transplant in 16 NDMM patients showed VGPR in 7, stringent complete response (sCR) in 4, partial response (PR) in 2 and CR in 3 patients (Sborov et al.). Grade 3 neutropenia was seen in 1 patient in this study. Richter et al, 2011 showed an ORR of 24% in 29 relapsed refractory multiple myeloma (RRMM) patients with Vor only regimen. Another study (Kaufmann et al., 2012) with Vor only regimen used in 10 RRMM patients showed stable disease (SD) in 9 and minimal response (MR) in 1 patient. ORR of 65% was achieved in 31 RRMM patients receiving Vor in combination with doxorubicin & bortezomib (Vorhees et al, 2017). Thrombocytopenia & neutropenia were reported in 94% and 59% patients respectively. Ricolinostat in combination with Rd and Vd achieved an ORR of 55% and 29% respectively in two studies with 38 and 57 evaluable patients (NCT01583283, NCT01323751). Another ricolinostat regimen with pomalidomide & dexamethasone achieved ≥PR in 6/11 RRMM patients (Madan et al., 2016). Table 1 illustrates the efficacy, number of patients and regimens used in all the studies in this systematic review. Quisinostat in a 2017 study by Moreau P et al. (NCT01464112) showed an ORR of 88% in a combination regimen with Vd in RRMM patients (N=18). Drug related adverse events were seen in 13 patients, thrombocytopenia being most common in 11 patients, 2 patients had grade 3 cardiac disorders and 1 patient had a cardiac arrest. Romidepsin in a phase I/II study (Harrison et al., 2011) combined with Vd was used in 25 RRMM patients. ORR was 60% with VGPR n=7, CR n=2, PR n=6, SD n=5 and PD n=1. Grade ≥3 thrombocytopenia in 16, neutropenia in 9 and peripheral neuropathy in 2 patients was seen. Popat et al used combination of two HDAC inhibitors CHR 3996 and tosedostat in 20 RRMM patients. ORR was 10% and SD was seen in 30% patients. Grade 3/4 toxicities seen were thrombocytopenia (n=12), leukopenia (n=6) and diarrhea (n=5). A phase I study on AR-42 drug in 17 RRMM patients (Sborov et al., 2017) showed SD in 10, PD in 4, MR in 3 patients with progression free survival (PFS) of 8.2 months. Thrombocytopenia, neutropenia and lymphopenia were seen in 11, 10 and 6 patients respectively. A detail of all grade 3 and higher adverse events along with dose limiting toxicity is given in table 2. Three trials (NCT02576496, NCT01947140, NCT03051841) of Edo-S101, romidepsin and CKD-581 are currently recruiting with 84, 93 and 18 planned number of patients. Conclusion Regimens containing vorinostat have shown an ORR up to 100% in NDMM patients. HDAC inhibitors have also shown promising efficacy up to 88% ORR in RRMM population. Majority of the patients developed cytopenias as hematological adverse events. Disclosures No relevant conflicts of interest to declare.

scholarly journals Phase I Study of Venetoclax Plus Daratumumab and Dexamethasone, With or Without Bortezomib, in Patients With Relapsed or Refractory Multiple Myeloma With and Without t(11;14)

2021 ◽  
pp. JCO.21.00443
Author(s):  
Nizar J. Bahlis ◽  
Rachid Baz ◽  
Simon J. Harrison ◽  
Hang Quach ◽  
Shir-Jing Ho ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Phase I ◽  
Phase I Study ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3

PURPOSE Venetoclax is an oral BCL-2 inhibitor with single-agent activity in patients with relapsed or refractory multiple myeloma (RRMM) with t(11;14) translocation. Venetoclax efficacy in RRMM may be potentiated through combination with agents including bortezomib, dexamethasone, and daratumumab. METHODS This phase I study ( NCT03314181 ) evaluated venetoclax with daratumumab and dexamethasone (VenDd) in patients with t(11;14) RRMM and VenDd with bortezomib (VenDVd) in cytogenetically unselected patients with RRMM. Primary objectives included expansion-phase dosing, safety, and overall response rate. Secondary objectives included further safety analysis, progression-free survival, duration of response, time to progression, and minimal residual disease negativity. RESULTS Forty-eight patients were enrolled, 24 each in parts 1 (VenDd) and 2 (VenDVd). There was one dose-limiting toxicity in part 1 (grade 3 febrile neutropenia, 800 mg VenDd). Common adverse events with VenDd and VenDVd included diarrhea (63% and 54%) and nausea (50% and 50%); grade ≥ 3 adverse events were observed in 88% in the VenDd group and 71% in the VenDVd group. One treatment-emergent death occurred in part 2 (sepsis) in the context of progressive disease, with no other infection-related deaths on study with medians of 20.9 and 20.4 months of follow-up in parts 1 and 2, respectively. The overall response rate was 96% with VenDd (all very good partial response or better [≥ VGPR]) and 92% with VenDVd (79% ≥ VGPR). The 18-month progression-free survival rate was 90.5% (95% CI, 67.0 to 97.5) with VenDd and 66.7% (95% CI, 42.5 to 82.5) with VenDVd. CONCLUSION VenDd and VenDVd produced a high rate of deep and durable responses in patients with RRMM. These results support continued evaluation of venetoclax with daratumumab regimens to treat RRMM, particularly in those with t(11;14).

A Phase I Study of Oral Melphalan Combined with LBH589 for Patients with Relapsed or Refractory Multiple Myeloma (MM).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1855-1855 ◽  
Author(s):  
James R. Berenson ◽  
Ori Yellin ◽  
Ralph V. Boccia ◽  
Youram Nassir ◽  
Shellie Rothstein ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Phase I ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Chemotherapeutic Agents ◽  
Treatment Schedule ◽  
Deacetylase Inhibitor ◽  
Previously Treated ◽  
Grade 3

Abstract Abstract 1855 Poster Board I-881 We and others have shown that LBH589, a potent histone deacetylase inhibitor (HDACi), significantly inhibits the growth of MM cells in vitro and enhances the cytotoxicity triggered by chemotherapeutic agents. Using our SCID-hu models of MM, we have also shown a striking inhibition of MM cell growth in vivo when LBH589 was combined with low doses of melphalan compared to treatment with either drug alone. Thus, these preclinical studies provided the rationale for evaluating the combination of oral melphalan with oral LBH589 for the treatment of MM patients with relapsed or refractory disease. We present the results of an ongoing phase I, open-label, multicenter, dose-escalation study. The initial treatment schedule involved administering patients oral LBH589 every Monday, Wednesday and Friday (MWF) combined with oral melphalan on days 1–5 of a 28-day cycle. Patients were to be treated to maximum response plus 2 additional cycles or complete 8 cycles of therapy without disease progression. To date, 15 patients have been enrolled. At study entry, eleven patients (73%) had International Staging System II or III MM. Fourteen patients were previously treated with melphalan. Three subjects were enrolled into the first cohort (oral LBH589 10 mg; melphalan 0.05 mg/kg) and all experienced significant hematological adverse events. During cycle 1, 2 of 3 subjects had grade 3 thrombocytopenia and all 3 patients developed grade 3 neutropenia. As a result, the melphalan dosing schedule was changed from being administered on days 1-5 to only on days 1, 3 and 5. Three subjects were enrolled into this modified first cohort using the same doses of both drugs. One subject in this cohort experienced both a grade 3 neutropenia and thrombocytopenia. However, there were no DLTs in this cohort and so enrollment into the next cohort (LBH589 at 20 mg and melphalan at 0.05 mg/kg) was initiated. In this cohort, one subject experienced a DLT (grade 4 thrombocytopenia) while the other two developed grade 3 thrombocytopenia. One patient achieved a immunofixation (IF)+ CR but withdrew consent due to intolerable fatigue. As a result, three additional patients were evaluated at this dose level, and two patients have responded including one active patient who is now in PR and another one also achieved a PR but had to be taken off study due to persistent grade 3 neutropenia. Based on the ongoing significant fatigue among patients treated with LBH89 throughout the treatment cycle, the protocol was revised so that the HDACi was administered only during the first two weeks (days 1, 3, 5, 8, 10, and 12) of the 28-day schedule. To date, 3 patients have recently started treatment with this modified schedule of LBH589 at 20 mg and melphalan at 0.05 mg/kg again administered on days 1, 3 and 5 of each 28-day cycle but are not yet evaluable for response. Thus, 12 patients are currently evaluable for response and 4 (33 %) who had previously received melphalan at higher doses have achieved a response including 1 complete response (IF+ CR) and 3 partial responses. Another 4 patients showed stable disease so that disease control was achieved overall in 8 (67%) patients. Overall, the most common ≥ grade 3 adverse events included reversible neutropenia and thrombocytopenia. Specifically, there were 6 cases of grade 3 neutropenia, 6 with grade 3 thrombocytopenia and 1 with grade 4 thrombocytopenia. All of these cytopenias were reversible. Because of the encouraging response rate (33%) that has already been observed in this relapsed and refractory population of heavily pretreated MM patients previously treated with melphalan, an expanded Phase II trial will be conducted using this combination once the MTD has been determined and schedule of dosing has been optimized. Disclosures: Berenson: Novartis Pharmaceuticals Corporation: Consultancy, Research Funding, Speakers Bureau. Off Label Use: LBH589 is a histone deacetylase inhibitor that is used for the treament of multiple myeloma. Rothstein:Novartis Pharmaceuticals Corporation: Employment.

A Prospective Randomized Phase I/II Study of Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) for Relapsed/Refractory Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2864-2864 ◽  
Author(s):  
Federica Cavallo ◽  
Alessandra Larocca ◽  
Maria Teresa Petrucci ◽  
Vincenzo Federico ◽  
Antonietta Pia Falcone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Phase I ◽  
Response Rate ◽  
Oral Prednisone ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3

Abstract Abstract 2864 Poster Board II-840 Background. New drug associations may improve patients outcome in relapsed/refractory multiple myeloma (MM). In newly diagnosed MM patients the addition of lenalidomide or thalidomide or bortezomib, to the standard oral melphalan and prednisone combination significantly increased response rate and event-free survival, showing synergistic effects. Aims. This is a multicenter, randomized, open label phase I/II trial designed to evaluate the safety/efficacy profile of the salvage treatment, Lenalidomide, Melphalan, Prednisone and Thalidomide (RMPT) in patients with relapsed/refractory myeloma. Methods. Oral lenalidomide was administered at 10 mg/day on days 1-21, in combination with oral melphalan at 0.18 mg/kg on days 1–4 and oral prednisone at 2 mg/kg on days 1–4. Thalidomide was administered at 50 mg/day (Arm A) or 100 mg/day (Arm B) on days 1-28. Each course was repeated every 28 days for a total of 6 courses. Maintenance therapy included Lenalidomide alone at 10 mg/day on days 1-21. Aspirin 100 mg/day was given as a prophylaxis for thrombosis. Results. Forthy-four patients with relapsed/refractory MM were enrolled in the study between May 2007 and March 2008, including 22 patients in arm A and 22 patients in arm B. After a median of 5 cycles 75% of patients achieved at least a partial response (PR), including 20% very good partial response (VGPR) and 14% near or complete response (nCR or CR). Among patients who received thalidomide 100 mg, the PR rate was 82% (including 23% VGPR and 23% CR/nCR). Higher response rate was observed among patients who received RMPT in first relapse. The 1-year-progression-free survival was 51,5% and the 1-year survival from study entry was 72%. Hematologic toxicity was the most frequent adverse event. Grade 3-4 hematologic adverse events included: neutropenia (68%), thrombocytopenia (36%) and anemia (32%). Grade 3-4 non hematologic adverse events included: infections (22,7%), neurological toxicity (4,5%) and fatigue (6,8%). No grade 3-4 thromboembolic events were reported. Conclusion. This is the first trial exploring the association of two immunomodulatory drugs, Thalidomide and Lenalidomide. RMPT is an active regimen in patients with relapsed/refractory MM. Toxicities were manageable and the incidence of neutrotoxcities was low. Updated results will be presented at the time of the meeting. Disclosures: Cavallo: CELGENE: Honoraria. Petrucci:CELGENE: Honoraria. Canepa:CELGENE: Honoraria. Boccadoro:CELGENE: CONSULTANCY, ADVISORY COMMITTEES, Research Funding. Palumbo:CELGENE: Honoraria.

Immunochemotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Fludarabine (F), Cyclophosphamide (C) and MabCampath (Cam) (FCCam) in Previously Untreated Patients (pts) with Advanced B-Chronic Lymphocytic Leukemia (B-CLL) : Experience On Safety and Efficacy within a Randomised Multicenter Phase III Trial of the french Cooperative Group On CLL and WM (FCGCLL/MW) and the “Groupe Ouest-Est d'Etudes Des Leucémies Aigües Et Autres Maladies Du sang” (GOELAMS) : CLL2007FMP (for fit medically patients).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 538-538 ◽  
Author(s):  
Stephane Lepretre ◽  
Therese Aurran ◽  
Beatrice Mahe ◽  
Bruno Cazin ◽  
Olivier Tournihlac ◽  
...  
Keyword(s):  
Adverse Events ◽  
Response Rate ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
Safety Analysis ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Number Of Patients ◽  
Grade 3 ◽  
11Q Deletion

Abstract Abstract 538 Introduction: Recent data suggest that FCR immunochemotherapy improves response rates and Progression-Free Survival (PFS) of previously untreated CLL pts. The monoclonal antibody alemtuzumab, a humanized anti-CD52 antibody (Campath), has shown activity alone and in combination in CLL pts. In order to validate the place of Campath in combination with the synergic association FC, the FCGCLL/MW and the GOELAMS conducted a multicenter French and Belgian phase III trial, CLL2007FMP, to evaluate the efficacy and toxicity of FCCam versus FCR in previously untreated patients with advanced CLL. PFS was the primary-end-point of this trial. Methods and Patients: A cohort of 178 fit medically pts (cumulative illness rating scale (CIRS) score of up to 6), less than 65 years old, without 17p deletion, were enrolled between November 2007 and January 2009. Pts were randomly assigned to receive 6 oral courses of FC (F 40mg/m2 d1-3 and C 250 mg/m2 d1–3; q 28 days) in combination with either R (n=83; 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent cycles; q 28 days) or Cam (n=82; 30 mg s/cut d1-3; q 28 days). Patients were stratified according to IgVH mutational status and 11q deletion. Anti-infective prophylaxis included trimethoprim-sulfamethoxazole and valaciclovir during immunochemotherapy and until the CD4-positive lymphocyte count reached 0,2 109/l. In the FCCAm arm, CMV monitoring was monthly performed by either PCR or antigenemia. The use of GSCF was recommended. The trial's recruitment was stopped in January 2009 after 165 pts had been randomized (83 and 82 respectively in the FCR and FCCam arms) because of an excess of mortality in the FCCam arm, while 13 patients were enrolled but not randomized because of this decision. Results: We reported here a preliminary analysis including baseline characteristics and response rates in the first 100 included pts but safety analysis of the whole cohort ; among the first 100 pts, 81% were Binet B, 19 % Binet C ; median age was 56.8 years (range 52.8 to 60.6). Percentages of pts with 11q deletion, unmutated IgVH status, and elevated β2m, were 18.5%, 48.4%, and 77.6%, respectively. A number of 76.5% (FCR arm) and 71.4% (FCCam arm) of pts received 6 cycles. Reasons for discontinuation were mainly related to persistent grade 3-4 neutropenia. Safety analysis data were availabel for 165 pts. Number of patients reported with Common Toxicity Criteria (CTC) grade 3-4 adverse events were observed in 87.8% (FCCam arm) versus 90.2% (FCR arm) (p = 0.76). Grade 3-4 neutropenia was the most frequently reported adverse event (79.6% with FCCam and 74.6% with FCR arm). Interestingly, percentage of observed grade 4 neutropenia was stable during FCR treatment (17.6% for cycle 1 and 17.9% for cycle 6) but increased during FCCam treatment (28.4% for cycle 1 and 45.5% for cycle 6). A total of 63 Serious Adverse events (SAE) were declared (19 with 18 pts in FCR arm, and 44 with 35 pts in FCCam arm) consisting mostly of the cases in febrile neutropenia (13 with FCR arm, 27 with FCCam arm); 7 patients died, all in the FCCam arm : 3 of B diffuse large B-cell lymphoma (one of them EBV positive), 1 of mucormycosis, 1 of septic shock due to P.aeruginosae and 2 of heart failure during neutropenia. The Overall Response Rate ( ORR) in the first 100 patients was 96% in the FCR arm compared to 85% in the FCCam arm (p=0.086). The Complete Response rate was 78% (FCR arm) versus 58% (FCCam arm) (p=0.072). PFS and OS are not yet evaluable. Conclusion: the FCCam regimen for the treatment of advanced CLL appeared to be associated with an unfavourable safety profile representing a significant limitation of its use in this indication. Other combinations with Alemtuzumab may be studied. Disclosures: No relevant conflicts of interest to declare.

A phase II trial of concurrent chemoradiaiton with paclitaxel/carboplatin in high-risk cervical cancer patients after radical hysterectomy: A multicenter prospective Korean study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5598-5598
Author(s):  
T. Lee ◽  
S. Kang ◽  
Y. Kim ◽  
B. Park ◽  
Y. Kim ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Radical Hysterectomy ◽  
Disease Free Survival ◽  
Side Wall ◽  
Treatment Schedule ◽  
Number Of Patients ◽  
Grade 3

5598 Background: In 1999, five randomized studies demonstrated that cisplatin based chemoradiation had a benefit over radiotherapy in cervical cancer. However, paclitaxel has been known to be safe and effective as a radiosensitizer, and carboplatin to be less toxic than cisplatin with simpler administration. Therefore, the object of this study was to evaluate the 2 year disease free survival and toxicity of high risk cervical cancer patients who received chemoradiation with paclitaxel/carboplatin. Methods: Seventy-one patients with at least one high risk factor after radical hysterectomy (metastasis to pelvic lymph nodes (LNs), invasion of parametrial tissue (PMs), positive vaginal resection margin) were administered 135 mg/m2 of paclitaxel, carboplatin (AUC = 5) every 3 weeks for 3 cycles as an adjuvant treatment. Radiotherapy was concomitantly administered to the whole pelvic region in 28 fractions totaling 4.5∼5.4Gy. Results: Median age was 49 (range: 26–80). Seven women were dropped from the study due to noncompliance and two patients did not complete treatment due to anaphylactic shock and prolonged infection. In total, sixty-two patients completed the protocol treatment. Of 211 chemotherapy cycles administered, grade 3 or 4 neutropenia occurred in 85 (40.3%) and the majority were transient. Dose reductions were in 7 cycles due to prolonged (over 4 days) neutropenia (6), and elevated liver enzyme (1). Febrile neutropenia occurred in only two patients. 14 patients experienced grade 3 or 4 non-hematologic toxicities: 1 sensory neurotoxicity, 2 fatigue, 4 diarrhea, 3 allergic reaction, 2 genitourinary, 2 hepatic, with no treatment related deaths. With a median follow-up of 20.1 (16–28) months, 8 patients experienced recurrences, 2 distant lung metastasis and 6 pelvic side wall or paraaortic recurrences (DFS: 87.1%, 95CI:78.8∼95.4). Conclusions: Concurrent chemoradiation with paclitaxel/carboplatin is well tolerated and appears effective in early stage high risk cervical cancer patients. Considering the advantages of lower toxicity and shorter treatment schedule, this regimen shows promise and should be further tested on a larger number of patients with a prolonged follow-up. No significant financial relationships to disclose.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

scholarly journals Concurrent chemoradiotherapy with S-1 compared with concurrent chemoradiotherapy with docetaxel and cisplatin for locally advanced esophageal squamous cell carcinoma

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xi-Lei Zhou ◽  
Chang-Hua Yu ◽  
Wan-Wei Wang ◽  
Fu-Zhi Ji ◽  
Yao-Zu Xiong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Grade 3

Abstract Background This retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2 twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups. Results A total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%, p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%, p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%, p = 0.275). Conclusion CCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

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