Phase II study to evaluate the efficacy of capecitabine combined with bevacizumab as first-line treatment in elderly patients with advanced or metastatic colorectal adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4119-4119
Author(s):  
J. Feliu ◽  
M. Safont ◽  
A. Salud ◽  
F. Losa ◽  
C. García-Girón ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Venous Thrombosis ◽  
Phase Ii ◽  
Colorectal Adenocarcinoma ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Open Label ◽  
Free Survival ◽  
Open Label Phase ◽  
Hand Foot Syndrome

4119 Background: Colorectal adenocarcinoma is the most common cancer in subjects over 70 years old. New therapies have been developed but limited data about their activity are available in elderly population. Results obtained with capecitabine have shown an appropriate safety and efficacy profile in these patients. The aim of the present study is to evaluate the overall response rate in that patient's population who presents colorectal adenocarcinoma and are treated with the combination of capecitabine+BVZ. Methods: This is a multicentric, non-controlled, open label, phase II clinical trial. Capecitabine(1250mg/m2 bid, orally)+BVZ(7.5mg/kg, intravenously) treatment was administered in 3-week length cycles until disease progression. Capecitabine dose was reduced to 1000mg/m2 when the creatinine clearance was between 30 and 50ml/min. Results: A total of 59 patients were included (57.6%, male). Mean age was 76±4.1 years. ECOG status was 0–1 in 96.5 % of the patients. Activities of daily living: moderate to severe dependence and functional incapacity in 24.5% and 5.6% of the patients by Lawton and Barthel scales, respectively. Comorbidities: hypertension (61%), venous thrombosis (5.1%), cardiac disease (5.1%) and acute cerebrovascular accident history (3.4%). Metastases were detected in liver (84.7%), lung (45.8%), local/regional (18.6%) and other locations (5.1%). Mean number of cycles of capecitabine+BVZ was 6.8±6.1. Most frequent grade 3–4 toxicities observed were hand-foot-syndrome (18.6%), diarrhea (8.5%), deep venous thrombosis (6.8%), pain (5.1%) and mucositis (3.4%). Four patients died due to toxicity (mucositis, digestive hemorrhage, hematological toxicity and sepsis, respectively). Metastasis resection was performed in 10.2% of the patients. Treatment response was: 33.3% partial response and 59.0% stable disease. Median progression-free survival was 10.8 months. Conclusions: The combination capecitabine+BVZ in elderly patients appears to have a manageable safety profile and achieves promising results in terms of response rates and progression free-survival. No significant financial relationships to disclose.

Results of a Phase II Study of Lenalidomide in Combination with Rituximab for the Treatment of Indolent Non Follicular Non Hodgkin Lymphoma (NHL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1645-1645
Author(s):  
Stefano Sacchi ◽  
Samantha Pozzi ◽  
Marina Cesaretti ◽  
Luigi Marcheselli ◽  
Eliana Valentina Liardo ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Conflicts Of Interest ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Open Label ◽  
Free Survival ◽  
Small Series

Abstract Abstract 1645 Background: Indolent non follicular B-Cell Lymphomas (INFL) are an eterogenous group of lymphomas and include small lymphocityic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL). Relapsed INFLs in advanced stage have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Lenalidomide (R®) is an immunomodulatory drug with effects on the innate immune system that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL. Methods: Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R® 20 mg once daily on days 1–21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R® when given in combination with R and to assess the safety of R2 evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were progression free survival (PFS), event free survival (EFS) and duration of remission (DR). Results: From July 2010 and June 2012, 39 patients were enrolled: 19 had SLL, 11 had LPL, 4 splenic MZL, 3 extranodal MZL and a 2 nodal MZL. Median age was 68 years (51–76) and 58% were male. LDH value was increased in 17% of pts and β-2-microglobulin in 87%; 41% of pts had Hb<12 g/dL and 62% were bone marrow positive. At time of current analysis treatment and response data were available in 27 pts. Overall treatment was completed in 18 pts (67%); in 9 cases treatment was interrupted prematurely primarily due to hematological toxicity (n=5) and due to disease progression (n=4). Of the 27 pts, 5 achieved a complete remission and 9 a partial remission with an ORR of 52%. In general, the regimen R2 was relatively well-tolerated. Grade 3–4 hematological events included neutropenia occurring in 50% of pts, infection in 7% and piastrinopenia in 3%. Growth factors were administered in 60% of pts. The median dose intensity was 0.94 for R and 0.92 for R®. With a median follow-up of 13 months (range 1–36), overall 9 pts had a lymphoma progression and 2 of them died. The 1-year overall survival and the 1-year PFS were 92% (IC95% 57–99%) and 78 months (IC95% 54–91%) respectively. Conclusions: In our trial follicular histology was an exclusion criteria and all pts were relapsed/refractory to immuno-chemotherapy rituximab-containing regimens. Thus the results observed with the chemo-free R2 scheme compare favorably with other previously reported results observed in relapsed indolent lymphoma treated with standard immuno-chenotherapy. Further the R2 combination was relatively well tolerated. In conclusion our results, although obtained in a small series of patient are encouraging and support further evaluation of R2 scheme in a larger cohort of patients. Disclosures: No relevant conflicts of interest to declare.

CTIM-30. PHASE II TRIAL OF PEMBROLIZUMAB IN RECURRENT AND RESIDUAL HIGH-GRADE MENINGIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi57-vi57
Author(s):  
Priscilla Brastianos ◽  
Albert Kim ◽  
Anita Giobbie-Hurder ◽  
Eudocia Quant Lee ◽  
Nancy Wang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
High Grade ◽  
Open Label ◽  
Free Survival ◽  
Significance Level ◽  
Open Label Phase ◽  
Immunosuppressive Tumor Microenvironment

Abstract INTRODUCTION High-grade meningiomas are associated with significant neuro-cognitive morbidity and a poor prognosis. Systemic therapies, to date, have demonstrated minimal efficacy. We recently found that high-grade meningiomas harbor an immunosuppressive tumor microenvironment and that programmed cell death-ligand 1 (PD-L1) expression may contribute to the aggressive phenotype of these tumors. Therefore, we conducted a single-arm, open-label phase II trial evaluating efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 24 patients with recurrent and progressive grade II and III meningiomas. METHODS The primary endpoint was the rate of progression-free survival at 6 months. The trial distinguished between 6-month PFS (PFS-6) rates of 26% vs. 52%. If at least 10 patients demonstrated a 6-month PFS, among the 24 patients, the agent would be considered worthy of further study. This design has at least 88% power using an exact binomial test with a one-sided significance level of 0.1. RESULTS Between November 2017 to December 2019, twenty-four patients were enrolled. The majority of the patients in our cohort were heavily pre-treated; prior to enrolling to the study, twenty patients underwent more than one surgical resection and twelve patients had received more than one round of radiotherapy. Our study met its primary endpoint and achieved a 6-month progression-free survival rate of 0.50 (90% exact CI: 0.32-0.68) and a median PFS of 8.3 months (90% CI: 4.1-12.9 months). For the twelve patients who achieved the PFS-6 primary endpoint, median PFS from the start of treatment was 17.3 months (90% CI: 9.7 – 24.3 months). Four patients had grade-3 or higher adverse events that were at least possibly treatment-related, including colitis, skin infection, encephalopathy and transaminitis. CONCLUSION Our study achieved its primary endpoint. These results suggest that pembrolizumab exerts promising activity on these tumors and results in prolonged PFS compared to historical controls.

An open-label, phase II trial of nanoparticle albumin bound paclitaxel (nab-paclitaxel), carboplatin, and bevacizumab in first-line patients with advanced non-squamous non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7610-7610 ◽  
Author(s):  
C. Reynolds ◽  
D. Barrera ◽  
D. Q. Vu ◽  
R. Jotte ◽  
A. I. Spira ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Santa Monica ◽  
Open Label Phase ◽  
Study Completion ◽  
Grade 3

7610 Background: The development of nab-paclitaxel has circumvented many of the infusion difficulties that are associated with standard solvent based paclitaxel (in cremophor). In this open label, phase II trial, patients with advanced (stage IIIB or IV) nonsquamous NSCLC received the combination of nab-paclitaxel, carboplatin and bevacizumab. Methods: 50 patients were enrolled between October 2005 and April 2006. Patients received intravenous (IV) nab-paclitaxel 300 mg/m2, carboplatin IV AUC=6, and bevacizumab 15 mg/kg on day 1 of each 21-day cycle. Responding patients received at least 4 cycles of treatment; however, therapy was discontinued for patients with progression or intolerable toxicity. The primary endpoint was response rate based on RECIST. Results: The median patient age was 67 years; 80% were white and 56% were female. Patients received a median of 4 cycles (range, <1–6). The preliminary efficacy results are PR 30% and SD 48%; no complete responses were noted. Median progression-free survival was 7.1 months (range, <1–10.6); median survival has not yet been reached. Grade 3–4 treatment related toxicities were neutropenia (52%); fatigue (19%); neuropathy (15%); thrombocytopenia (10%) dyspnea (6%), anorexia, constipation, febrile neutropenia, hemoptysis, and nausea and/or vomiting (4% each). 64% of patients are currently alive. 32 patients have come off study, prior to 4 cycles due to disease progression (12%), adverse event (10%), investigator request (8%), sudden death (6%), and withdrawal of consent (2%); 16 patients had normal study completion (completed 4 cycles of therapy). Conclusions: This combination of nab-paclitaxel, carboplatin and bevacizumab was well tolerated, with moderate neutropenia. Adverse events were manageable. The preliminary analysis from this study indicates that this combination has promising activity in first-line patients with non-squamous NSCLC. This research was supported, in part, by a research grant from Abraxis BioScience, Inc., Santa Monica, CA. No significant financial relationships to disclose.

Phase II Study of Uracil-Tegafur With Leucovorin in Elderly (≥ 75 years old) Patients With Colorectal Cancer: ECOG 1299

2007 ◽  
Vol 25 (34) ◽  
pp. 5397-5402 ◽  
Author(s):  
Howard S. Hochster ◽  
Weixiu Luo ◽  
Elizabeta C. Popa ◽  
Bruce T. Lyman ◽  
Mary Mulcahy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Survival Time ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Old Patients ◽  
Gi Toxicity ◽  
Grade 3

Purpose To evaluate the tolerability and effectiveness of uracil-tegafur (UFT) with leucovorin (LV) in the treatment of elderly patients with advanced colorectal cancer. Patients and Methods Patients ≥ 75 years of age with previously untreated colorectal cancer were eligible for this phase II, single-arm, open-label, multicenter cooperative group clinical trial. UFT 100 mg/m2 plus LV 30 mg orally every 8 hours for 28 days every 35 days was administered until progression. Results Fifty-eight patients were enrolled between June 2000 and July 2001, and 55 were treated. The median age of treated patients was 81 years (range, 75 to 90 years), 26 patients were (47%) women, and 80% had good performance status (0 to 1). The observed overall response rate was 22% (95% CI, 11.8% to 35.0%). The estimated median overall survival time was 13.0 months (95% CI, 9.6 to 17.4 months), and median progression-free survival time was 4.6 months (95% CI, 2.6 to 6.7 months). Among the 56 treated patients (including one ineligible patient), 31 (55%) experienced grade 3 to 4 toxicities, most commonly diarrhea (25%) and GI toxicity (36%), with patients older than 85 years of age at highest risk. Conclusion The results of this trial support the efficacy of oral UFT/LV in elderly patients with colorectal cancer. The regimen is tolerated moderately well overall, particularly as compared with other fluoropyrimidine regimens, although there is increased GI toxicity in the most elderly. These results suggest that studies using newer oral fluoropyrimidine analogs should be investigated in this patient population.

Silmitasertib (CX-4945) in combination with gemcitabine and cisplatin as first-line treatment for patients with locally advanced or metastatic cholangiocarcinoma: A phase Ib/II study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 312-312
Author(s):  
Mitesh J. Borad ◽  
Li-Yuan Bai ◽  
Ming-Huang Chen ◽  
Joleen M. Hubbard ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Preliminary Evidence ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Phase Ib ◽  
Open Label Phase ◽  
Almost All

312 Background: Silmitasertib (CX-4945), an oral small molecule inhibitor of casein kinase 2 (CK2), has exhibited preclinical antitumor activity and strong synergism with gemcitabine + cisplatin. We investigated the safety and efficacy of silmitasertib in combination with gemcitabine + cisplatin in patients with unresectable cholangiocarcinoma (CCA). Methods: S4-13-001 is a multicenter, open-label, phase Ib/II study of silmitasertib in combination with gemcitabine + cisplatin in patients with locally advanced or metastatic CCA. The phase Ib portion included dose-escalation, expansion, and exploratory cohorts of silmitasertib with doses ranging from 200 to 1000 mg bid (6 days for the escalation/expansion cohorts and 10 and 21 days’ continuous dosing for the exploratory cohorts). In the phase II portion patients received silmitasertib 1000 mg bid for 10 days in combination with gemcitabine + cisplatin on days 1 & 8 over a 21-day cycle. In this interim analysis, we present findings from the combined population of patients from the phase Ib and II portions of the study. Response to treatment was assessed by RECIST v1.1 every 6 weeks. Primary efficacy outcome measure was progression-free survival (PFS). ClinicalTrials.gov (NCT02128282). Results: A total of 87 patients were enrolled and received silmitasertib in the phase Ib (n=50) and phase II (n=37) portions of the study. Of these, 55 patients were evaluable for efficacy with details as follows: median PFS 11.1 (95% CI 7.6–14.7) months; median overall survival (OS) 17.4 (95% CI 13.4–25.7) months; overall response rate (ORR) 32.1%; and disease control rate (DCR) 79.3%. Almost all patients (79/87; 90.8%) evaluable for safety reported ≥1 treatment-related adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib were diarrhea (65.5%), nausea (50.6%), vomiting (33.3%), fatigue (31.0%), and anemia (21.8%). The most common grade ≥3 TEAEs were diarrhea (13.8%), neutropenia (11.5%), nausea (9.2%), anemia (8.0%), and thrombocytopenia (8.0%). Eleven patients (12.6%) discontinued treatment due to TEAEs. Conclusions: Silmitasertib in combination with gemcitabine + cisplatin yields promising preliminary evidence of efficacy in patients with locally advanced or metastatic CCA. Based on these data a randomized phase III trial is planned. Clinical trial information: NCT02128282.

Biweekly Raltitrexed in Combination with Irinotecan (RIR) as Second-Line Therapy for Patients with Metastatic Colorectal Cancer: A Non-Randomized, Open-Label Phase II Trial.

2020 ◽  
Author(s):  
Ke Cheng ◽  
Yu-Wen Zhou ◽  
Ye Chen ◽  
Zhi-Ping Li ◽  
Meng Qiu ◽  
...  
Keyword(s):  
Adverse Events ◽  
Overall Response Rate ◽  
Progression Free Survival ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Free Survival ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

Abstract Background Irinotecan-based doublet chemotherapy strategy was standard second-line backbone treatment for patients with oxaliplatin‑refractory metastatic colorectal cancer(mCRC). The aim of this study was to evaluate tolerability and efficacy of raltitrexed combined with irinotecan biweekly administered as the second-line therapy for mCRC patients.Methods The study was a single-center, non-randomized, open-label phase II trial. Patients with mCRC after failure with first-line treatment of oxaliplatin and fluoropyrimidine or its derivatives were enrolled. Irinotecan (180 mg/m2) and raltitrexed (2.5 mg/m2) were given intravenously on day 1. Cycles were repeated every 2 weeks. The primary endpoint was progression-free survival, and the secondary endpoints included overall response rate, disease control rate, overall survival and treatment related adverse events. Results Between December 2012 and October 2016, 35 patients were enrolled. 33 and 35 patients were assessed for response and safety, respectively. The overall response rate (ORR) was 8.6 %, and the disease control rate (DCR) was 71.4%. The median progression-free survival (PFS) was 4.5 months (95% CI 3.8–5.2). The median overall survival was 12.0 months (95% CI 8.5–15.5). Four patients received conversion therapy to no evidence of disease (NED), and 2 patients were still alive with beyond 24 months survival. The most common grade 3/4 hematological adverse events were leukopenia (8.6%), neutropenia (5.7%). The most common grade 3/4 nonhematological adverse events were anorexia (14.3%), vomiting (14.3%), nausea (11.4%) and fatigue (8.6%). Two patients discontinued the protocol treatment because of treatment-related gastrointestinal adverse events. No one died from treatment-related events. The incidence and severity of toxicity was irrelevant to UGT1A1 status.Conclusions The combination of irinotecan with raltitrexed is an active, convenient and acceptable toxic regimen for second-line treatment for mCRC patients, which needs further study as a chemotherapy backbone to be combined with targeted agents in mCRC.Trial registration No. ChiCTR-ONC-12002767. The study was registered with the Chinese Clinical Trial Registry at 29 Octorber 2012, http://www.chictr.org.cn/index.aspx.

scholarly journals Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation

2020 ◽  
Vol 38 (13) ◽  
pp. 1378-1388 ◽  
Author(s):  
Eileen M. O’Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Open Label ◽  
Free Survival ◽  
Palb2 Mutation

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.

Phase II study of ifosfamide, carboplatin and etoposide (ICE) in recurrent glioblastoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2066-2066
Author(s):  
T. Aoki ◽  
K. Nojima ◽  
T. Mizutani ◽  
M. Ishikawa ◽  
A. Takasu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Secondary Endpoints

2066 Background: To evaluate the efficacy and tolerability of ifosfamide, carboplatin and etoposide ( ICE ) in patients with recurrent glioblastoma. Methods: This was an open-label, single-center phase II trial. Forty-two patients with first recurrent glioblastoma after surgery, standard radiotherapy and a first-line temozolomide-based or ACNU-based chemotherapy, were enrolled.The primary endpoint was progression-free survival at 6 months ( PFS-6 ), and secondary endpoints were response rate, toxicity, and survival. Chemotherapy consisted of Ifosfamide ( 700 mg / m2 on day 1, 2 and 3 ), carbopaltin ( 100 mg / m2 on day 1 ), etoposide ( 70 mg / m2 on day 1, 2, and 3 ), every 6 weeks. Results: PFS-6 was 37 %. The median PFS was 17 weeks. Response rate was 27 %. Adverse events were generally mild ( grade 1 or 2 ) and consisted mainly of alopecia. Conclusions: This regimen is well tolerated and has activity in patients with recurrent glioblastoma. No significant financial relationships to disclose.

A randomized, open label, prospective study comparing the association between sorafenib (So) and interleukin-2 (IL-2) versus So alone in advanced untreated renal cell cancer (RCC): Rosorc Trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5099-5099
Author(s):  
G. Procopio ◽  
E. Verzoni ◽  
S. Bracarda ◽  
S. Ricci ◽  
C. Sacco ◽  
...  
Keyword(s):  
Disease Control ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Antitumoral Activity ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Open Label Phase ◽  
Hand Foot Syndrome ◽  
Tumour Shrinkage

5099 Background: So is an orally active multikinase inhibitor with a well documented activity in advanced RCC. IL-2 is a pleiotropic cytokine with antitumoral activity depending on dose and schedule. The aim of the study is to evaluate the activity and the safety of So and IL-2 association compared to So alone. Methods: In this multicenter, randomized, open label, phase II study, 128 previously untreated metastatic RCC patients (pts) were randomized to receive 400 mg of So, orally given twice daily continuously, in combination with IL-2, 4.5 MIU administered subcutaneously, five times a week for six consecutive weeks any eight weeks (arm A), or So alone (arm B) at the same dose. Therapy continued until progression of disease or unacceptable toxicity. The primary end point was progression free survival (PFS) and the secondary endpoints were response rate, safety and overall survival. Eligible pts had histological diagnosis of RCC, ECOG 0–2, no brain metastases, measurable disease and any Motzer's score. Pts were stratified according to different histotypes and Motzer's score. Results: All pts were enrolled from October 2006 to February 2008. Response rates (all partial responses, PR) were 23 % and 10 % in arm A and B respectively. Overall disease control rates (PR + stable disease SD) were 81 % versus 74 %. Tumour shrinkage was reported in 52 % and 34 % of arm A and B therapies respectively. Median PFS was 38 weeks (range 6–104+) for So + IL-2 and 30 weeks (range 6–102+) for So alone. PFS at 1 year was 31% in the combination therapy versus 22% in arm B. The most common adverse events (AEs) were asthenia, hand foot syndrome, hypertension, fever, diarrhoea and mucositis. AE were usually low or moderate in severity and always reversible and manageable. Grade 3–4 AE were reported in 33% and 22% in arm A and B, respectively. Conclusions: The safety and efficacy data suggest that the association So + IL-2 is safe and feasible and, compared to So alone, improves tumour shrinkage, disease control rate and PFS. [Table: see text]

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