Pemetrexed and carboplatin in the treatment of malignant pleural mesothelioma (MPM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18114-18114
Author(s):  
M. Papi ◽  
G. Genestreti ◽  
D. Tassinari ◽  
E. Tamburini ◽  
S. Nicoletti ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Locally Advanced ◽  
Median Number ◽  
Hematological Toxicity ◽  
Complete Regression ◽  
Progression Of Disease ◽  
Localized Disease ◽  
Grade 3 ◽  
Vitamin B12 Supplementation ◽  
Unacceptable Toxicity

18114 Background. MPM is a poor prognosis disease, whose clinical negative outcome is due both to it’s aggressiveness and to the lack of active drugs for clinical practice. To assess activity and safety of pemetrexed-carboplatin combination in the treatment of MPM, an open trial has been recently concluded in our departments. Methods. All the consecutive patients with proven diagnosis of MPM admitted to our departments between 2003 and 2005 were considered eligible and enrolled into the trial. All the patients were treated with pemetrexed 500mg/m2 and carboplatin AUC 5mg/ml/minute every 21 days until progression of disease or unacceptable toxicity. All the patients were treated with steroid prophylaxis, folinic acid and vitamin B12 supplementation. Results. 26 patients (18 chemotherapy-naive) were considered eligible and enrolled into the trial. 21 patients were male and 5 female; median age of the patients was 67 years (range 49–77). 22 patients were affected by locally advanced or extensive disease and the other 4 ones by localized disease. All the patients were valuable for response, toxicity and survival. Overall response rate was 19,3%, with 5 partial responses and no complete regression of the disease. A stable disease was observed in 7 patients (26.9%), with an overall disease control rate of 46.2%. 201 complete courses of chemotherapy was performed with a median number of 6 courses/patients. Toxicity was mild with grade 3/4 WHO neutropenia in 4 patients (15.3%), grade 3 anemia and thrombocytopenia in 2 patients (7.6%). No grade 3/4 non-hematological toxicity was observed along all the conduction of the trial. Median survival was 9,3 months, assessed with the Kaplan Meyer non-parametric test. Conclusions. Pemetrexed and carboplatin seem to represent an active and well tolerated schedule against MPM, confirming their priority role in the treatment of the disease; nevertheless, further trials are probably needed to improve the outcome of chemotherapy in this rare poor-prognosis disease. Supported by IOR No significant financial relationships to disclose.

Immune checkpoint inhibition (ICI) in combination with SBRT in patients with advanced pancreatic adenocarcinoma (aPDAC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 192-192 ◽  
Author(s):  
Gagandeep Brar ◽  
Changqing Xie ◽  
Charalampos S. Floudas ◽  
M. Pia Morelli ◽  
Suzanne Fioravanti ◽  
...  
Keyword(s):  
Partial Response ◽  
Locally Advanced ◽  
Primary Objective ◽  
Clinical Activity ◽  
Correlative Analysis ◽  
Progression Of Disease ◽  
New Treatment ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

192 Background: Chemotherapy in aPDAC has resulted in only modest improvements in outcome. The effectiveness of ICI monotherapy is also limited in PDAC, suggesting an immunogenic inert tumor microenvironment. SBRT is safe and effective in locally advanced PDAC and exhibits enhanced antitumor immunity. We hypothesize that ICI plus SBRT will improves immunomodulatory effects of ICI in patients with aPDAC resulting in a greater clinical benefit. Methods: Eligible patients with aPDAC were enrolled to four different treatment cohorts. Cohort 1: Durvalumab (Durva) 1500 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 2: SBRT 5 fractions x 5Gy followed by Durva. Cohort 3: Durva + Tremelimumab (Treme) 75 mg every 4 weeks + SBRT 1 fraction x 8Gy on day 1. Cohort 4: SBRT 5 fractions x 5Gy followed by Durva + Treme. This was continued until unacceptable toxicity or progression of disease. A biopsy was performed at baseline and pre-cycle 2 of treatment for exploratory correlative analysis. The primary objective was to evaluate the safety and feasibility of combining ICI and SBRT to enhance the efficacy of ICI. Results: 51 patients with aPDAC were enrolled and 31 patients were evaluable for the efficacy. The most commonly TRAEs were lymphopenia. Grade 3-4 AEs were lymphopenia and anemia. No dose limiting toxicities were seen. Out of total 31 evaluable patients, 1 patient achieved a confirmed partial response seen in Cohort 1 and 2 patients in Cohort 4, and 7 stable disease across the 4 treatment arms. Median PFS and OS was 1.7 months (95% CI 0.7-2.8 months) and 3.4 months (95% CI 0.9-11.4 months) in cohort 1; 2.6 months (95% CI 2.1-4.7 months) and 9.1 months (95% CI 3.4-18.7 months)in cohort 2; 1.6 months (95% CI 0.5-4.0 months) and 3.0 months (95% CI 0.7-6.6 months) in cohort 3; and 3.2 months (95% CI 1.5-16.5months) and 6.4 months (95% CI 1.5-17.6 months) in cohort 4. Conclusions: The combination of ICI and SBRT is safe and well tolerated in patients with aPDAC. The overall response rate of 9.6% including 2 patients who achieved a durable partial response lasting over 12 months, suggests meaningful clinical activity. This signifies that ICI and SBRT is a potential new treatment for aPDAC. Clinical trial information: NCT02311361.

Bendamustine Salvage Therapy for T-Cell Non Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4860-4860
Author(s):  
Francesco Zaja ◽  
Luca Baldini ◽  
Stefano Luminari ◽  
Andrés J.M. Ferreri ◽  
Alberto Grossi ◽  
...  
Keyword(s):  
T Cell ◽  
Hodgkin Lymphoma ◽  
Target Therapy ◽  
Active Agent ◽  
Response Duration ◽  
Median Number ◽  
Hematological Toxicity ◽  
Cell Transplant ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

Abstract Abstract 4860 Background At present, the standard salvage treatment for relapsed/refractory (R/R) T-cell non Hodgkin lymphoma (NHL) has not been defined yet. Several studies indicated the high therapeutic activity and good safety profile of Bendamustine in B-cell NHL while, on the contrary, only few data are available in T-cell NHL. Recently, a multicenter phase II study showed that Bendamustine is active in angioimmunoblastic lymphoma and other T-cell NHL with 50% overall response rates (OR) and 28% complete responses (CR) (Gressin et al. J Clin Oncol, 2012 ASCO Annual Meeting Proceedings, 30, 15 suppl: 8026). Purpose On this basis we evaluated in the contest of everyday clinical practice the efficacy and safety of Bendamustine salvage monotherapy in unselected adult patients with T-cell NHL. Patients and Methods Hematological and Oncological Italian centers involved in the treatment of patients with lymphomas were asked to report retrospectively the results of their experience regarding the use of Bendamustine in T-cell NHL. Response status and toxicity were evaluated according to Cheson 2007 and to the Common Terminology Criteria For Adverse Events V 4.0. Results Clinical data of 20 patients with R/R T-cell NHL (median age 73 years, range 31–83; 14 males) treated with Bendamustine in seven Italian centers between March 2009 and June 2012 were analyzed. Investigated series included 6 peripheral T-NHL-NOS, 4 angioimmunoblastic (AILT), 3 prolymphocytic T-cell leukemia (PLL), 3 advanced- stage Mycosis Fungoides (MF)/Sezary Syndrome (SS), 2 large granular lymphocyte (LGL) NHL and 2 ATLL- like HLTV-1 negative NHL. The median interval from diagnosis to Bendamustine treatment was 18 months (range 1–74). Eleven patients received up to 2 previous lines of therapy, while 9 received more than 2, including CHOP or CHOP-like therapy (14 patients), Fludarabine or Pentostatine (5), Gemcitabine based therapy (7), Alemtuzumab (4), Romidepsin (1), allogeneic stem cell transplant (1). Nearly 70% of patients were refractory to the last previous chemotherapy. Bendamustine was given as monotherapy at a dosage of 60 and 70 mg/m2 (7 patients) or 90–100 mg/m2(13) for a median number of 2.5 cycles (range 1–8) and a total number of 67 cycles. Response to Bendamustine was CR in 2 (10%) and PR in 8 (40%), with an ORR of 50%, including 3 PR in T-cell NHL/NOS, 1 CR in AILT, 3 PR in PLL, 1 PR in MF/SS, 1 CR and 1 PR in LGL NHL. The median period of observation was 6 months (range 1–18 months); 6- months estimated PFS, OS and response duration are 63%, 70% and 60%, respectively. Three patients in PR (2 PLL and 1 MF) progressed after 3, 4 and 7 months. Grade 3–4 neutropenia, thrombocytopenia and anemia were registered in 44%, 25% and 19% of cases. Three patients developed pneumonia (1 invasive aspergillosis) and 1 had septic shock; no grade 3–4 extra hematological toxicity was reported. Conclusions Bendamustine is a safe and active agent that desertes further investigation in patients with T-cell NHL. Combinations with other cytostatics or target therapy with potential synergistic effect should be assessed in future prospective trials. Disclosures: Zaja: Mundipharma: Honoraria. Off Label Use: Bendamustine In T-NHL. Fanin:Mundipharma: Honoraria.

A phase I clinical study of biweekly carboplatin and gemcitabine in patients with advanced solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12024-12024
Author(s):  
P. Kumar ◽  
M. Keshtgarpour ◽  
H. Kumar ◽  
A. Dudek
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Hematological Toxicity ◽  
Ecog Performance Status ◽  
Primary Tumors ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Tumor Types ◽  
Dose Levels

12024 Background: Carboplatin (CBDCA) and gemcitabine (GEM) in combination is used commonly in lung cancer and is administered on a 21 day cycle. The purpose of this study was to determine the maximum tolerated dose (MTD) of CBDCA and GEM administered on a biweekly schedule and to assess safety and efficacy of this schedule. Methods: GEM was given intravenously (IV) over 30 minutes followed by CBDCA also given IV over 30 minutes. This combination was given on day 1 every 2 weeks. The dose levels examined are shown in the Table . A total of 26 patients were studied (18 male, 8 female) with median age of 56 (range 41–83 years); ECOG performance status of 24 patients were 0 (5), 1 (16), 2 (2), 3 (1); prior chemotherapy ranged from 0 to 4 regimens; median number of cycles administered per patient was 3 (range 1–9) with a total of 81 cycles. The primary tumors were lung (11), melanoma (4), head and neck (3), squamous cell penile/toe (2), bladder (2), kidney (1), gastric (1), esophageal (1) and ovary (1). Results: No DLTs were seen in any of these patients and the MTD was not reached. Delay in treatment was seen in total of 6 cycles due to myelosuppression and 1 cycle due to nausea and anorexia. Grade 3/4 hematological toxicity rates: anemia - 3/81 cycles (3.7%), neutropenia - 20/81 cycles (25%), and thrombocytopenia - 4/81 cycles (5%). Non-hematological toxicity was mild. The median time to progression was 40 days (range 4–133) and of 18 evaluable patients partial response or stable disease was seen in 7 (38.8%). Conclusions: Even at maximum tested dose of GEM at 2000 mg/m2 and CBDCA at AUC of 3.0, this schedule is well tolerated. Hematological toxicity such as neutropenia and thrombocytopenia was minimal. We plan to study this schedule of GEM and CBDCA in appropriate tumor types in combination with biologic agents. [Table: see text] [Table: see text]

Topotecan (T) and carboplatin (C) in the treatment of platinum sensitive relapsed ovarian cancer (ROC): Results of a multicenter phase I/II study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5089-5089
Author(s):  
D. Koensgen ◽  
A. Belau ◽  
P. Klare ◽  
T. Steck ◽  
O. Camara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Remission Rate ◽  
Primary Standard ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Median Number ◽  
Hematological Toxicity ◽  
Platinum Sensitive ◽  
Grade 3

5089 Background: Despite of the effectiveness of radical surgery and first-line chemotherapy, most patients (pts) with advanced ovarian cancer will relapse. Paclitaxel (P) in combination with C as second-line treatment improves the outcome of pts with platinum-sensitive ROC in comparison to C monotherapy. Due to polyneuropathy and alopecia this regimen can not be offered to all pts. Therefore, other platinum-combinations are required. We conducted a phase I/II study to define the dose limiting toxicities (DLT) and the tolerability of combination therapy with T and C. Methods: Pts with platinum-sensitive ROC and primary standard therapy were stratified according to treatment-free interval (TFI): 6–12 months (A) and ≥12 months (B). Following dose regimens were analysed: T 1mg/m2/d1–3 + C AUC5/d3 and T 0.75 mg/m2/d1–3 + C AUC5/d3, q21d. DLT was based on the first 4 courses and defined as: CTC grade 3/4 hematological and grade 2 non-hematological toxicity (excepted alopecia, vomiting), treatment delay >7d. Primary endpoints were DLT and tolerability. Secondary endpoints were remission rate (RR) and progression-free survival (PFS). Results: From 06/04 to 08/05, 28 pts were enrolled, 26 pts (A:13 pts, B:13 pts) were eligible. Median age was 61.5 years. A total of 141 cycles were analysed, median number of cycles was 6 (range A:2–8, B:1–10). DLTs were: leucopenia (n = 5) and thrombocytopenia (n = 1). MTD was reached at dose: T: 0.75mg/m2 and C: AUC5. Overall, grade 3/4 hematologic toxicities (in% of all cycles), for (A) and (B) respectively, were: anemia 4% vs. 4%, leucopenia 34% vs. 13%, neutropenia 30% vs. 31%, thrombocytopenia 7% vs. 6%. Febrile neutropenia 4.3% vs. 0%. Darbepoetin alfa was given in 13.5% of all cycles. Overall, grade 3/4 non-hematologic toxicities were infrequent (< 5%). Overall RR (95% CI) was 50% (29.7–70.1) [A: 30.8% (0.1–61.1), B: 69.3% (38.7–90.9)]. Median follow-up was 5.8 mo, median PFS (95% CI) was 7.7 mo (1.3–9.4) [A: 6.2 (1.3–7.2), B: 8.0 (7.3–9.4)]. Median overall survival was not reached. Conclusions: TC is a feasible and effective chemotherapy regimen for platinum sensitive ROC. Tolerability is not associated to TFI. The recommended dose for subsequent studies is T:0.75 and C:AUC5. No significant financial relationships to disclose.

Induction chemotherapy with S-1 plus cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15501-15501
Author(s):  
J. Chung ◽  
Y. Choi ◽  
H. Shin ◽  
G. Choi ◽  
W. Lee ◽  
...  
Keyword(s):  
Performance Status ◽  
Locally Advanced ◽  
Local Treatment ◽  
Complete Response ◽  
Hematological Toxicity ◽  
Common Grade ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
And Performance ◽  
Mild Toxicity

15501 Background: This study was to assess the efficacy and safety profiles of the combination treatment with S-1 and Cisplatin in patients with locally advanced SCCHN. Methods: Eligible patients were defined as histologically confirmed SCCHN, stage III or IV with no evidence of distant metastasis, evaluable lesions, adequate organ function, age of 20–80 years, and performance status 0,1 or 2. Cisplatin was infused over 1 hour on day 1 (75 mg/m2) and S-1 was administered orally for 14 consecutive days (day 2–15). The dosages of S-1 were assigned according to the patients’ body surface area (BSA): 50 mg twice a day (BSA < 1.5m2), 60 mg twice a day (BSA > 1.5m2). Each course was repeated every 3 weeks. After 2 course, tumor response were evaluated by CT scan and laryngoscopy. If the patients achieved a response (complete response: CR, or partial response: PR), they received one more course of chemotherapy before undergoing the radiotherapy or operation as a definitive local treatment. Results: All 22 patients were assessable for response and toxicity. The overall response was 80.9% (CR: 3, PR: 14). The adverse reactions occurred 120 times in 54 courses of 22 cases. The most common grade 3/4 adverse events were neutropenia, which occurred in 8 patients. Non-hematological toxicity of grade 3 and 4 included nausea and vomiting in 4 patients, fever in one patient and, fatigue in one patient. Since the observation period is short, the analysis about survival rate is not obtained so far. Conclusions: S-1 plus Cisplatin combination chemotherapy is effective against locally advanced SCCHN with mild toxicity. No significant financial relationships to disclose.

Randomized multicenter phase III trial of oxaliplatin plus raltitrexed compared to oxaliplatin plus fluorouracil and leucovorin treatment in recurrent and metastatic colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4102-4102
Author(s):  
J. Wang ◽  
J. Li ◽  
S. Qin ◽  
T. Liu ◽  
Z. Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Median Number ◽  
Disease Control Rate ◽  
Phase Iii ◽  
Progression Of Disease ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps

4102 Purpose: To compare oxaliplatin (L-OHP) plus raltitrexed (RTX) with L-OHP plus fluorouracil and leucovorin (LV/5FU) for patients (pts) with recurrent and metastatic colorectal cancer(CRC). Methods: Eligible pts had to have histologically proven recurrent or metastatic CRC,not having previously received oxaliplatin as palliative chemotherapy,ECOG PS = 2,age:18∼70,and adequate hematological,renal and hepatic function.After written informed consent,pts were randomized to L-OHP:130 mg/m2 d1 + RTX: 3 mg/m2 d1 (Arm A) or + LV: 200 mg/m2 + 5FU:375 mg/m2 d1–5 (Arm B). Results: Between Jan 2005 and July 2006, 216 pts were enrolled at 15 centers in China.112 pts (mean age: 55.0 (19∼70), M/F: 57/46, PS 0/1/2: 46/53/13) were randomly assigned to A and 102 (mean age: 54.2(22∼70), M/F: 54/46, PS 0/1/2: 44/59/9) to B. 203 pts were eligible for response evaluation (A:103, B:100).The median number of cycles was 4 (1∼6) in A and 3 (1∼6) in B (P=0.1431).The RR was 29.1% (CR:2, PR:28, SD:50 , PD:23) in A and 17.0% (CR:2, PR:15, SD:46 , PD:37) in B (P=0.0437).The disease-control rate was 77.7% in A and 63.0% in B (P=0.0237). After a median follow-up of 10 months (4–16.5),92 pts had had progression of disease (40 in A and 52 in B); 73 deaths had occurred (35 in A and 38 in B), median time to progression was not reached. Following-up is ongoing.The median QoL scores for the two arms were comparable. 214 were included in the safety analyses (A:112, B:102). There was a higher incidence of neutropenia (48.2% verse 29.4%, P=0.005) and transaminase increase (49.1% verse 35.3%, P=0.041) among A. Grade 3 or 4 neutropenia was much common in pts in A than those in B (20.5% verse 4.9% , P=0.001), but was complicated by fever in only 3.6% of cases (4 pts) in A and in 2.9% of cases (3 pts) in B. No pts were dead or infectious due to neutropenia. There were similar rates of grade 3 or 4 transaminase elevation in the two groups. Vomitting and anorexia were much commoner with B. Conclusions: The L-OHP+RTX seems beneficial in recurrent and metastatic CRC, demonstrating better response rate and higher disease control rate with acceptable tolerability, maintenance of QoL and convenient administration schedule. No significant financial relationships to disclose.

A phase I/II study of concurrent nab-paclitaxel, carboplatin, and IMRT for locally advanced squamous cancer of the head and neck (LASCCHN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5579-5579
Author(s):  
Roy B. Tishler ◽  
Jochen H. Lorch ◽  
David J Sher ◽  
John Ross Clark ◽  
Annie W Chan ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Locally Advanced ◽  
Median Number ◽  
Weekly Chemotherapy ◽  
Locoregional Treatment ◽  
Normal Tissue Toxicity ◽  
Optimal Dosing ◽  
Squamous Cancer ◽  
Grade 3

5579 Background: We studied escalating doses of weekly nab-paclitaxel (Abraxane, AB) combined with weekly carboplatin (CP) and daily IMRT in patients with LASCCHN to determine the safety and optimal dosing of AB. The favorable biodistribution of AB, an albumin bound formulation of paclitaxel, may allow for intensified locoregional treatment without increasing normal tissue toxicity. Methods: An AB dose escalation was performed, initially using concurrent weekly CP (AUC = 1.5), Erbitux (ER) and daily IMRT to 70 Gy. After ER was dropped, dose escalation of AB from 20 mg/m2 to 50 mg/m2 was performed in 10 mg/m2 increments using a 3 + 3 study design. Results: A total of 28 patients have enrolled and all have completed treatment. Patients ranged in age from 42 to 72 years old (median = 59), with follow up from 3 to 48 months (median = 25). Most patient had oropharyngeal primaries (n=22) and stage III (n=8) or IV (n=20) disease; 18 were HPV+, 6 HPV- and 4 unknown. Initially 6 patients received weekly AB (20 mg/m2), ER and CP, but ER was dropped due to greater than anticipated mucositis and dysphagia. Subsequently, 3 patients each received CP with AB at 20, 30 and 40 mg/m2 weekly and a total of 13 received CP with AB at 50 mg/m2. The median radiation dose is 70 Gy and the median number of weekly chemotherapy cycles is 7. The primary toxicities were Grade 3 dysphagia, mucositis and dermatitis in 24 of 28 patients. Only 3 (of 28) PEG tubes remain at 4, 6 and 14 months. No DLTs were observed at any dose level. There have been 5 recurrences, with 4 being local-regional. Two patients have died of disease and 26 are alive. Conclusions: Concurrent AB, CP, and IMRT is a safe chemoradiotherapy combination in LASCCHN with early data demonstrating feasibility and efficacy.

Updated results from a randomized phase II dose-ranging study of the JAK2-selective inhibitor SAR302503 in patients with myelofibrosis (MF).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7109-7109 ◽  
Author(s):  
Animesh Dev Pardanani ◽  
Catriona H. M. Jamieson ◽  
Nashat Y. Gabrail ◽  
Claudia Lebedinsky ◽  
Guozhi Gao ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Median Number ◽  
Randomized Phase Ii ◽  
Night Sweats ◽  
Dose Ranging ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Dose Reductions ◽  
Unacceptable Toxicity

7109 Background: We previously reported results of treating MF patients with 3 cycles of 300, 400, or 500 mg of SAR302503 (NCT01420770; Blood 2012;120:21 Abs 2837). This is a report of efficacy and safety after 6 cycles. Methods: Patients ≥18 years of age with intermediate-2 or high-risk MF and splenomegaly were eligible. SAR302503 is administered orally, once a day in consecutive 4-week cycles until disease progression or unacceptable toxicity. Spleen response (≥35% reduction in spleen volume vs baseline) was assessed by MRI/CT (blinded independent central review). Results: 31 patients were enrolled (n=10 in the 300 and 400 mg groups; n=11 to 500 mg). Risk status was balanced in all but the 300 mg group (70% high-risk). Most patients were JAK2V617F positive (90%) and blood transfusion independent (81%). Spleen response rates at the end of cycle (EOC) 6 (secondary end point) were 30% (3/10) in the 300 mg group, 60% (6/10) with 400 mg, and 55% (6/11) with 500 mg compared with EOC 3 rates of 30%, 50%, and 64%, respectively. One patient on 500 mg who had a spleen response at EOC 3 (39% reduction), but not at EOC 6 (25% reduction) had dose reductions to 200 mg due to anemia. Median number of cycles was 13 (range, 2–17) and 24 patients have been on treatment >12 months. SAR302503 reduced baseline constitutional symptoms at the EOC 3, with the greatest responses for night sweats in 14/15 patients (93%), itching 10/14 (71%), early satiety and abdominal pain, each in 10/18 (56%). Most common adverse events were anemia and diarrhea, with grade 3–4 rates of 58% and 13%, respectively. The rate of grade 3–4 thrombocytopenia was 16%. There was no grade 3–4 neutropenia. The diarrhea rate tended to decrease after the first 2 treatment cycles. There have been no reports of withdrawal syndrome after stopping SAR302503. Median JAK2V617F allele burden was 93% at baseline, 87% at the EOC 3, and 78% at EOC 6 in 19/26 patients who had available samples. The expression of 22 of 97 cytokines was significantly regulated (≥1.5 fold difference; p<0.05) after cycle 1. Conclusions: In this Phase II trial, continued treatment with SAR302503 was associated with clinically meaningful reductions in splenomegaly. Symptom data will be updated. Clinical trial information: NCT01420770.

A dose-escalation phase I study of a first-in-class cancer stemness inhibitor in patients with advanced malignancies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2542-2542 ◽  
Author(s):  
Adrian Langleben ◽  
Jeffrey G. Supko ◽  
Sebastien J. Hotte ◽  
Gerald Batist ◽  
Hal W. Hirte ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Cancer Stemness ◽  
Advanced Malignancies ◽  
Progression Of Disease ◽  
Excellent Safety Profile ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

2542 Background: Cancer Stem Cells (CSC) are considered to be fundamentally responsible for malignant growth, relapse, metastasis, and resistance to conventional therapies. BBI608 is an orally-administered first-in-class cancer stemness inhibitor which blocks CSC self-renewal and induces cell death in CSC as well as non-stem cancer cells by inhibition of the Stat3, Nanog and b-catenin pathways, and has shown potent anti-tumor and anti-metastatic activities pre-clinically. Methods: A phase 1 dose escalation studyin adult patients with advanced cancer who had failed standard therapies was conducted to determine the safety, tolerability, recommended phase 2 dose (RP2D), pharmacokinetics and preliminary anti-tumor activity of BBI608. A modified Simon accelerated titration scheme was used for dose escalation, with a cycle consisting of twice-daily oral administration of BBI608 for 4 weeks. Cycles were repeated every 4 weeks (28 days) until progression of disease, unacceptable toxicity, or other discontinuation criteria were met. Results: Fourteen cohorts (N=41) were dosed from 20 mg to 2000 mg/day with adverse events being generally mild; the most common being grade 1-2 diarrhea, nausea, anorexia and fatigue. Four grade 3 events included diarrhea (n=3) and fatigue (n=1). MTD was not reached and further dose escalation was limited by pill burden. By the 400 mg/day dose level the plasma concentration of BBI608 was sustained for over 8 hours at a concentration above 1.5 uM (several fold above the IC50). 17/26 patients evaluable for tumor response achieved SD, for a DCR of 65%. Prolonged TTP was observed in 12/26 evaluable patients (46%), including patients with colorectal (CRC), head and neck, gastric, ovarian, melanoma, and breast cancer. In the subset of patients with CRC (N=18), SD was seen in 8/12 evaluable (67%). A median PFS of 14 weeks and median OS of 47 weeks were observed in evaluable CRC patients. Conclusions: Dose escalation of BBI608, a first-in-class cancer stem cell pathway inhibitor, has been achieved without dose limiting toxicity. BBI608 has shown an excellent safety profile, favorable pharmacokinetics, and encouraging signs of clinical activity particularly in CRC Clinical trial information: NCT01775423.

Retrospective review of modified dose docetaxel, cisplatin, and 5-flourouracil (DCF) for the treatment of first-line metastatic gastric carcinomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15175-e15175
Author(s):  
Nuriye Özdemir ◽  
Sercan Aksoy ◽  
Tulay Eren ◽  
Huseyin Abali ◽  
Omur Berna Oksuzoglu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Retrospective Review ◽  
Progression Free Survival ◽  
Complete Response ◽  
Metastatic Gastric Cancer ◽  
Median Number ◽  
Hematological Toxicity ◽  
First Line ◽  
Gastric Carcinomas ◽  
Grade 3

e15175 Background: Docetaxel, cisplatin, and 5FU (DCF) has been shown to be an effective regimen for metastatic gastric carcinomas. However, treatment-related adverse events is quite high with original dose DCF. We evaluated the outcomes of the metastatic gastric carcinomas who treated with modified dose DCF (mDCF) in our institution. Methods: A single institution retrospective review of patients with metastatic gastric cancer treated with three weekly mDCF from 1/2006 to 1/2013 was evaluated. Over this time period a standard order-set was in place in which cisplatin 60 mg/m2, 5FU 600 mg/m2 and docetaxel 60 mg/m2 was given three weekly. Tumor response was calculated retrospectively using RECIST criteria. Results: One hundred and ninety-one patients were included the study. The median age was 55 years (23 to 76), 74% were male, and 82% were chemo-naive. Eighty percent of the patients were metastatic at the time of diagnosis. The median number of cycles administered was 6 (2-10). Hematological toxicity was mild with grade 3/4 granulocytopenia in 25% of the patients, grade 3/4 thrombocytopenia in 4% of the patients, and grade 3/4 anemia in 9% of the patients. Neutropenic infection occurred in 9 (%5) patients. Grade 3/4 nausea/vomiting was reported by 10% of the patients, and diarrhea by 7%. A total of 19 (10%) patients had dose delays or dose reductions related to toxicity. Six (3%) patients had complete response and 43 (23%) patients had partial response. Stable disease were occurred in 83 (45%) patients and 56 (23%) progressive disease. Ninety percent of the patients have died with median follow-up of 8 months. Progression-free survival was 7 months (95% CI 6 to 7.8 m) and overall survival was 10 months (95% CI 8.7 to 11.2 m). Conclusions: mDCF has mild hematological toxicity and overall excellent tolerance in first line metastatic gastric cancer patients. Response rate and the survival of these patients with a minimal toxicity are comparable with the original dose DCF.

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