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.

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.

PS02.101: PREOPERATIVE TREATMENT BASED ON THE DCF CHEMOTHERAPY AND SUPPORTIVE THERAPY FOR ESOPHAGEAL CANCER

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 149-150
Author(s):  
Shunsuke Tanabe ◽  
Yasuhiro Shirakawa ◽  
Naoaki Maeda ◽  
Takayuki Ninomiya ◽  
Kazuhiro Noma ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Clinical Stage ◽  
Supportive Therapy ◽  
Preoperative Treatment ◽  
Node Metastasis

Abstract Background The neoadjuvant chemotherapy using CDDP and 5-FU(CF) is the standard treatment for advanced esophageal cancer, defined as clinical stage II/III in Japan. However, more powerful chemotherapy has been required for the treatment of cases of cStageIII cases. In 2011, the combination treatment of CF and Docetaxel (DCF) was introduced for the treatment of those cases in our institute. DCF therapy increased chemotherapy remarkable cases. But, adverse events occur at high rates, including high myelosuppression. Therefore, it is necessary to ensure support by early intervention of supportive therapy so as not to exacerbate adverse events. We report about treatment outcome in preoperative DCF therapy cases. Methods We treated 128 esophageal cancer patients who underwent surgery following preoperative DCF therapy between 2011 and July 2017, and preoperative DCF was administered to 128 patients 2 course completely. The neoadjuvant chemotherapy regimen using DCF is Docetaxel:70mg/m2 (day1) + CDDP:70mg/m2 (day1) + 5-FU:700mg/m2 (day1–5). Results In the preoperative DCF group, overall response rate (over PR) was 51.5%. There were 37 cases in 128 cases of pathological tissue effect judgment for Grade 2 and 3. 14 cases of them (14cases/37cases:37.8%) had lymph node metastasis. Therefore it is necessary to control lymph node metastasis by surgery even in a remarkable group. Almost all patients experienced grade 4 adverse events, particularly neutropenia is a high frequency. From the start of chemotherapy, pretreatment of intraoral infection lesion and prevention and treatment of oral mucositis are performed. Considering the degree of myelosuppression during initial chemotherapy, in the second course, we actively administer G-CSF preparation. Conclusion A good prognosis can be expected if preoperative DCF therapy is effective. It is necessary to perform intensive and safe preoperative chemotherapy with appropriate supportive therapy intervention. Disclosure All authors have declared no conflicts of interest.

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.

VS01.05: RADICAL OPERATION OF ESOPHAGEAL CANCER UNDER 2D THORACOSCOPE

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 44-45
Author(s):  
Jie Jiang ◽  
Xiuyi Yu ◽  
Guojun Geng ◽  
Hongming Liu
Keyword(s):  
Esophageal Cancer ◽  
Conflicts Of Interest ◽  
Radical Surgery ◽  
Basic Operation ◽  
Radical Operation ◽  
Operation Procedure

Abstract Description To The basic operation procedure of esophageal cancer radical surgery. Disclosure All authors have declared no conflicts of interest.

PS02.231: RELATIONSHIP BETWEEN CHANGE IN TONGUE PRESSURE AND PNEUMONIA AFTER ESOPHAGECTOMY

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 187-188
Author(s):  
Aya Yokoi ◽  
Daisuke Ekuni ◽  
Reiko Yamanaka ◽  
Manabu Morita
Keyword(s):  
Esophageal Cancer ◽  
Postoperative Complications ◽  
Body Temperature ◽  
Conflicts Of Interest ◽  
Invasive Procedure ◽  
Portable Device ◽  
Postoperative Pneumonia ◽  
Tongue Pressure ◽  
White Blood Count ◽  
Swallowing Function

Abstract Background Esophagectomy for esophageal cancer is a highly invasive procedure with several serious postoperative complications, including pneumonia. It is commonly accepted that deteriorated swallowing function causes postoperative pneumonia. However, measurement to evaluate swallowing function related to postoperative pneumonia has not been developed. Recently, it became possible to measure tongue pressure using a non-invasive, easy and portable device. We hypothesized that tongue pressure relates to postoperative pneumonia. The aim of this study was to investigate the relationship between change in tongue pressure and pneumonia after esophagectomy among inpatients with esophageal cancer. Methods Fifty-eight inpatients (39 males and 19 females; 33–77 years old) who underwent esophagectomy participated in this study. Measurement of tongue pressure was performed using a portable device before esophagectomy (baseline) and at postoperative 1 and 2 weeks. Repetitive saliva swallowing test (RSST) was also performed to evaluate swallowing function at the same time. Pneumonia was postoperatively diagnosed by the chest X-ray, white blood count, body temperature and purulent sputum. The data of general and oral conditions were collected from medical and dental records. Data also included sex, age, type of cancer, cancer stage (International Classification of Diseases for Oncology ICD-10 version 2015), type of operation (thoracotomy or thoracoscopy), type of preoperative chemotherapy, surgical duration, amount of bleeding during surgery, type of reconstruction, incidences of postoperative complications, intubation period, body temperature, blood chemical analysis, health behaviors and oral condition. Differences in parameters between the pneumonia (+ ) group (n = 10) and pneumonia (-) group (n = 48) were analyzed by Mann-Whitney U or Chi-square test. Level of significance was set at P < 0.05. Results Tongue pressure significantly decreased after esophagectomy (P < 0.05). The decrease in tongue pressure, age, amount of bleeding during surgery, length of fasting days, the ratio of thoracotomy and aspiration in the pneumonia (+ ) group were significantly greater than those in the pneumonia (-) group (P < 0.05). Conclusion The decrease in tongue pressure was related to the incidence of pneumonia after esophagectomy among inpatients with esophageal cancer. Disclosure All authors have declared no conflicts of interest.

Efficacy and safety results from GEICO 1205, a randomized phase II trial of neoadjuvant chemotherapy with or without bevacizumab for advanced epithelial ovarian cancer

2019 ◽  
Vol 29 (6) ◽  
pp. 1050-1056 ◽  
Author(s):  
Yolanda Garcia Garcia ◽  
Ana de Juan Ferré ◽  
Cesar Mendiola ◽  
Maria-Pilar Barretina-Ginesta ◽  
Lydia Gaba Garcia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Debulking Surgery ◽  
Randomized Phase Ii ◽  
Interval Debulking Surgery ◽  
Grade 3 ◽  
Macroscopic Response

BackgroundBevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery.ObjectiveTo evaluate neoadjuvant bevacizumab in a randomized phase II trial.MethodsPatients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery.ResultsOf 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery.ConclusionsAdding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.

RA02.08: SALVAGE LYMPHADENECTOMY FOR 14 PATIENTS OF ESOPHAGEAL CANCER AFTER DEFINITIVE CHEMORADIOTHRAPY

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 22-22
Author(s):  
Kazuki Odagiri ◽  
Makoto Yamasaki ◽  
Koji Tanaka ◽  
Yasuhiro Miyazaki ◽  
Tomoki Makino ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Lymph Nodes ◽  
Conflicts Of Interest ◽  
Treatment Guideline ◽  
Hospital Death ◽  
Curative Surgery ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Salvage Lymphadenectomy

Abstract Background Salvage Lymphadenectomy is regarded as the only curative surgery to residual or recurrence lymph nodes of esophageal cancer after definitive chemoradiotherapy (dCRT). However, salvage lymphadenectomy is not described in the Japanese esophageal cancer treatment guideline because of little evidences for the safety and efficacy. Methods From January 2011 to December 2015, we performed 14 salvage lymphadenectomies to residual or recurrence LN of esophageal squamous cell carcinoma(ESCC) in Osaka University. We assessed postoperative complications and long-term outcome. Results Average age was 64 year-olds (SD: 5.2). Male: Female = 11: 3. cStage I: II-IV = 7: 7. Surgery to cervical LN were 11 patients and abdominal LN were 3 patients. Surgery to residual LN (res-LN) were 9 patients and recurrence LN (rec-LN) were 5 patients. rec-LN patient's median time to recurrence after dCRT was 14.3 months (10.2–29.3). 4 patients were performed lymphadenectomy resecting with adjacent organs, 3 patients were bronchus (trachea? ) and 1 patient was right subclavian artery. 4 patients had postoperative complication, two were pneumonia, one was pulmonary thrombosis and one was lymphorrhea, but there was no serious case (Clavien-Dindo Grade II or less). We didn’t have hospital death. Six of 14 patients had recurrence and died after salvage lymphadenectomy. Recurrence sites were 2 mediastinal lymph nodes and liver, lung, loco-regional and peritoneal. But no patients had recurrence of main tumor. 5-year overall survival rate was 51.1%. Median survival time in 9 patients, surgery to res-LN, was 18.9 months (10.4–132 months) and 5 patients, surgery to rec-LN, was 4.9 months (1.4–26.6 months). Surgery to res-LN patients were longer than rec-LN patients in overall survival after salvage lymphadenectomy (P = 0.395). There was no difference due to the difference in recurrence site of the cancer in overall survival after salvage lymphadenectomy. Conclusion Our data show salvage lymphadenectomy safety and effectiveness after dCRT. Salvage lymphadenectomy may extend the prognosis of patients with esophageal cancer after dCRT. Thus, salvage lymphadenectomy may be one of the treatment options for the patients with residual or recurrent, especially the former, lymph node after definitive CRT, although it is necessary to evaluate in many cases. Disclosure All authors have declared no conflicts of interest.

Randomized study of the effect of synbiotics during neoadjuvant chemotherapy on adverse events in esophageal cancer patients

2017 ◽  
Vol 36 (1) ◽  
pp. 93-99 ◽  
Author(s):  
Masaaki Motoori ◽  
Masahiko Yano ◽  
Hiroshi Miyata ◽  
Keijiro Sugimura ◽  
Takuro Saito ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Adverse Events ◽  
Cancer Patients ◽  
Randomized Study

Adding Mercaptopurine and Methotrexate to Alternate Week ATRA Maintenance Therapy Does Not Improve the Outcome for Adults with Acute Promyelocytic Leukemia (APL) in First Remission: Results From North American Leukemia Intergroup Trial C9710

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 258-258 ◽  
Author(s):  
Bayard L. Powell ◽  
Barry K Moser ◽  
Wendy Stock ◽  
Robert E. Gallagher ◽  
Cheryl L Willman ◽  
...  
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Risk Group ◽  
Statistical Significance ◽  
Phase Iii ◽  
Consolidation Therapy ◽  
Number Of Patients ◽  
First Remission ◽  
Grade 3

Abstract Abstract 258 This randomized phase III clinical trial was designed to evaluate the potential benefit and toxicity of (a) arsenic trioxide (ATO) as initial consolidation therapy and (b) maintenance therapy with oral tretinoin (ATRA) either alone or together with 6-mercaptopurine (MP) and methotrexate (MTX) in newly diagnosed patients with APL. All patients received induction therapy with ATRA, daunorubicin (DNR) and cytarabine. Adults (≥ 15 years) were randomized at study entry to receive a standard consolidation with 2 courses of ATRA plus DNR, or 2 courses of ATO as initial consolidation followed by 2 courses of ATRA plus DNR. Patients who remained in complete remission (CR; n=331) were then randomized (stratified by consolidation arm and age group) to one year of maintenance with ATRA alone (45 mg/m2/d) for 7 days repeated every other week (n=166) or in combination with MP 60 mg/m2/daily plus oral MTX 20 mg/m2/weekly (n=161). The target number of maintenance events was 146, and the study had 80% power to detect a hazard ratio of 1.6 at 5 years. We previously reported that the addition of ATO consolidation markedly improved event-free (EFS) and disease-free (DFS) survival (Blood 2010; 116:3751–3757). We now report the results of the maintenance randomization after a median follow up of 6.2 years. The two groups were well balanced by pretreatment characteristics. DFS, the primary endpoint, and overall survival (OS) were not statistically different for the two maintenance arms (log-rank p=0.14 and p=0.33, respectively). Evaluation by consolidation arm (by intention-to-treat, ITT) and by APL risk group also failed to demonstrate a significant advantage for either maintenance treatment. There was no interaction effect between consolidation and maintenance arms (p=0.78). Age, gender, CD56 expression and FLT3-ITD or TKD mutations at diagnosis did not have an impact on outcome by maintenance arm.ATRA*ATRA/MP/MTX*PDFS: overall41/16630/1610.14DFS by consolidation arm (ITT): ATO10/844/780.13no ATO31/8226/830.21DFS by risk group: low/intermediate25/12819/1300.20high16/3811/310.683-year DFS from CR79%87%0.056OS: overall22/16616/1650.33OS by consolidation arm (ITT): ATO8/843/810.15no ATO14/8213/840.72OS by risk group: low/intermediate14/1289/1340.20high8/387/310.733-year OS from study entry92%95%0.28*Number of events/number of patients in each group or subgroup. No treatment-related deaths were reported during maintenance therapy. Hematologic adverse events were more common in the combination arm (maximum grade 3/4, 18% vs 4%; p< 0.0001), as were non-hematologic adverse events (maximum grade 3/4, 36% vs 25%; p=0.033). Only 71 DFS events have occurred to date. Although the 3-yr DFS favors the combination arm, the differences in DFS and OS with the addition of MP and MTX to ATRA maintenance do not reach statistical significance. The addition of ATO consolidation therapy remains the most important determinant of DFS and OS for APL patients in first remission on this randomized trial. Among patients who were randomized to maintenance, only 5 patients who received ATO consolidation have relapsed – 2 from the combination arm and 3 from the ATRA alone arm. Relapse of APL is uncommon in patients who received ATO consolidation, and the need for any maintenance therapy in these patients has yet to be determined. Disclosures: Off Label Use: Arsenic trioxide as consolidation treatment for APL.

The Efficacy and Safety of Immunomodulatory Drugs in Multiple Myeloma Maintenance Therapy: Results of a Meta-Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3477-3477
Author(s):  
Yucai Wang ◽  
Fang Yang ◽  
Wenwen Zhang ◽  
Xiaoxiang Guan ◽  
Neil Kothari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Maintenance Therapy ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Immunomodulatory Drugs ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Abstract Objective: To evaluate the efficacy and safety of immunomodulatory drugs (IMiDs) in maintenance therapy of multiple myeloma through meta-analysis of randomized controlled trials (RCTs). Patients and methods: PubMed, Web of Science, ASCO, ESMO and ASH databases were searched for RCTs that investigated the treatment outcomes (overall survival [OS], progression-free survival [PFS] and/or event-free survival [EFS] and/or time to progression [TTP]) of maintenance therapy with IMiDs in patients with multiple myeloma. Study endpoints included OS, PFS/EFS/TTP, and grade 3 or 4 adverse events. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). The random-effect model was utilized in view of clinical heterogeneity in the study population. Results: Eighteen RCTs comprising a total of 6562 patients were included in this meta-analysis. IMiDs used in the RCTs included thalidomide (14 trials) and lenalidomide (4 trials). Overall, IMiD-based maintenance therapy significantly improved OS (HR = 0.91, 95% CI = 0.84 - 0.99, P = 0.027) and PFS (HR = 0.63, 95% CI = 0.60 - 0.68, P < 0.001). Notably, IMiDs maintenance therapy increased OS in the setting of ASCT but showed no OS prolongation without ASCT. On further stratification, thalidomide-based maintenance therapy demonstrated OS benefit only in the setting of ASCT, while lenalidomide-based maintenance therapy did not show OS benefit regardless of transplantation status. For PFS however, both thalidomide- and lenalidomide-based maintenance therapies demonstrated significant survival benefits, regardless of transplantation status (Table 1). IMiD-based maintenance therapy increased the risk of developing grade 3 or 4 neutropenia (RR = 3.04, 95% CI = 2.49 - 3.70, P < 0.001), thrombocytopenia (RR = 2.68, 95% CI = 1.90 - 3.79, P < 0.001), anemia (RR = 1.97, 95% CI = 1.23 - 3.15, P = 0.005), infection (RR = 1.53, 95% CI = 1.22 - 1.92, P < 0.001), fatigue (HR = 1.71, 95% CI = 1.24 - 2.36, P = 0.001), constipation (RR = 2.04, 95% CI = 1.15 - 3.62, P = 0.015), and peripheral neuropathy (RR = 2.02, 95% CI = 1.20 - 3.39, P = 0.008). Conclusions: IMiD-based maintenance therapy results in significant improvement in OS and PFS in multiple myeloma patients but increased the risk of developing some grade 3 or 4 adverse events. While thalidomide-containing maintenance therapy regimens showed OS benefits in the setting of ASCT, lenalidomide-containing maintenance therapy did not prolong OS regardless of transplantation status. Both thalidomide- and lenalidomide-based maintenance therapies increased PFS in multiple myeloma patients independent of transplantation status. When more data on lenalidomide and the newer agent pomalidomide become available, further analysis will be warranted to analyze the efficacy and safety of IMiDs in multiple myeloma maintenance therapy. Table 1. Effects of IMiD-based maintenance therapy on OS and PFS in multiple myeloma patients IMiD ASCT status Survival Number of trials HR 95% CI P value Thalidomide/Lenalidomide combined OS 18 0.91 0.84 - 0.99 0.027 with ASCT OS 10 0.88 0.78 - 0.99 0.036 without ASCT OS 9 0.94 0.83 - 1.06 0.299 Thalidomide combined OS 14 0.92 0.84 - 1.01 0.090 with ASCT OS 8 0.87 0.77 - 1.00 0.049 without ASCT OS 7 0.97 0.85 - 1.10 0.640 Lenalidomide combined OS 4 0.84 0.67 - 1.04 0.102 with ASCT OS 2 0.89 0.66 - 1.20 0.457 without ASCT OS 2 0.78 0.57 - 1.06 0.114 Thalidomide/Lenalidomide combined PFS 17 0.63 0.60 -0.68 < 0.001 with ASCT PFS 9 0.62 0.57 - 0.67 < 0.001 without ASCT PFS 9 0.66 0.60 - 0.73 < 0.001 Thalidomide combined PFS 13 0.67 0.63 - 0.72 < 0.001 with ASCT PFS 7 0.66 0.60 - 0.72 < 0.001 without ASCT PFS 7 0.69 0.62 -0.77 < 0.001 Lenalidomide combined PFS 4 0.50 0.43 - 0.58 < 0.001 with ASCT PFS 2 0.49 0.41 - 0.58 < 0.001 without ASCT PFS 2 0.52 0.40 - 0.67 < 0.001 Disclosures No relevant conflicts of interest to declare.

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