CTNI-02. NERATINIB FOR TREATMENT OF LEPTOMENINGEAL METASTASES FROM HER2-POSITIVE BREAST CANCER IN EXTENDED ACCESS PROGRAM: PRELIMINARY RESULTS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi58-vi58
Author(s):  
Alessia Pellerino ◽  
Rosa Palmiero ◽  
Francesco Bruno ◽  
Erminia Muscolino ◽  
Federica Franchino ◽  
...  
Keyword(s):  
Median Time ◽  
Progression Free Survival ◽  
Median Number ◽  
Her2 Positive ◽  
Neurological Improvement ◽  
Extended Access ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
Radiological Response ◽  
Investigational Agents

Abstract INTRODUCTION The aim of the study was to evaluate the activity of neratinib in LM from HER2-positive BC after the failure of multiple lines of treatment. PATIENTS AND METHODS Inclusion criteria were as follows: age ≥ 18 years; histological diagnosis of primary HER2-positive BC; newly-diagnosed LM (LANO criteria); KPS ≥ 60; coexistence of BM that have or not received radiotherapy; life expectancy ≥ 3 months; previous drugs, including capecitabine, trastuzumab, T-DM1, pertuzumab, and hormone therapy, were allowed, with the exclusion of lapatinib or other investigational agents. Neratinib was administered 240 mg daily continuously. Primary endpoint was the OS. Secondary endpoints were progression-free survival (PFS), neurological benefit, radiological response rate, and tolerability. RESULTS Nine patients with LM have been enrolled with a median age of 44 years, and a median KPS of 80. Median time since LM onset from the diagnosis of primary BC was 42 months, and patients underwent a median number of adjuvant treatments before LM of 3. Three patients developed LM alone, and other 6 had LM associated with multiple BM. Six-months and 1-year OS were 66.7% and 22.3%, respectively, with a median OS of 8 months (95%CI 3-13*). Median PFS was 3.5 months (95%CI 2-6) after the start of treatment. A neurological improvement was reported in 2/9 patients (22.2%), while in other 4/9 patients (44.5%) was achieved a neurological stabilization lasting for a median time of 5 months (95%CI 2-19). The best radiological response was a stable disease in 5/9 patients (55.6%), while no complete or partial were achieved according to LANO criteria. A CSF clearance was observed in 1 patient only (11.1%). Grade III-IV adverse events were not reported, and 2 patients only (22.2%) had mild diarrhea correlated with neratinib. CONCLUSIONS Neratinib might be a safe and effective treatment in LM from heavily pretreated HER2-positive BC.

HORIZON (OP-106): An exploratory analysis of time-to-next treatment (TTNT) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) who received melflufen plus dexamethasone (dex).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20570-e20570
Author(s):  
Maria-Victoria Mateos ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Blade ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Progression Free Survival ◽  
Staging System ◽  
Median Number ◽  
Ocean Study ◽  
Disease Stabilization ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
International Staging System

e20570 Background: Melflufen is a novel peptide-drug conjugate that rapidly delivers a cytotoxic payload into tumor cells. Melflufen + dex showed efficacy and a manageable safety profile in pts with poor-risk, heavily pretreated RRMM in the phase 2 HORIZON study (Mateos et al. ASH 2019. Abs. 1883). For pts with RRMM, longer TTNT is indicative of disease stabilization and clinical benefit and is associated with lower costs (Chen et al. J Manag Care Spec Pharm. 2017). This report of TTNT after melflufen + dex from HORIZON is, to our knowledge, the first report from a trial population with such advanced RRMM. Methods: Pts with RRMM who had received ≥2 prior lines of therapy, including an IMiD and a proteasome inhibitor (PI), and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody (mAb), received melflufen 40 mg (IV on d1 of each 28-d cycle) + dex 40 mg/wk until disease progression or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints included progression-free survival (PFS) and safety. TTNT was defined as the time from start of melflufen + dex to first subsequent therapy. Results: Overall, 154 pts were treated (data cutoff, Oct 1, 2019); median age was 64.5 y (range, 35-86), 32% had International Staging System stage 3 disease, 38% had high-risk cytogenetics, 32% had extramedullary disease (EMD), the median number of prior therapies was 5 (range, 2-12), and 71% had triple-class refractory MM (IMiD + PI + anti-CD38 mAb). Treatment discontinuation occurred in 108 pts (70%), most commonly due to disease progression (47%) and adverse events (14%). Among 125 pts evaluable for response, with a median follow up of 15.3 mo, the median TTNT was 8.0 mo (95% CI, 7.2-8.9) and the median PFS was 4.2 mo (95% CI, 3.7-4.9). TTNT and PFS were similar in subgroups of pts with triple-class refractory MM and EMD (Table). Subsequent therapies after melflufen + dex will be presented. Conclusions: TTNT in HORIZON (median 5 prior lines) was consistent with previous reports of TTNT in pts with RRMM who received melflufen + dex or other therapies (median 2-4 prior lines) (Bringhen et al. J Clin Oncol. 2019. Abs. 8043). Melflufen + dex is being further evaluated in the phase 3 OCEAN study (NCT03151811) in pts with RRMM who are refractory to lenalidomide. Clinical trial information: NCT02963493. [Table: see text]

P14.42 Neratinib for treatment of leptomeningeal metastases from HER2-positive breast cancer in extended access program: preliminary results

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii46-ii46
Author(s):  
A Pellerino ◽  
R Palmiero ◽  
F Bruno ◽  
F Mo ◽  
E Muscolino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Median Time ◽  
Systemic Disease ◽  
Progression Free Survival ◽  
Leptomeningeal Metastases ◽  
Her2 Positive ◽  
Poor Overall Survival ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer ◽  
Radiological Response

Abstract BACKGROUND Leptomeningeal metastases (LM) occur in 5% of human epidermal growth factor receptor 2 (HER2) breast cancer (BC) with a poor overall survival (OS) of 3 months. Neratinib is an oral, irreversible tyrosine kinase pan-inhibitor that was approved by FDA for the treatment of HER2-enriched BC, who completed a prior adjuvant trastuzumab-based therapy. The aim of the study was to evaluate the activity of neratinib in LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab. PATIENTS AND METHODS Inclusion criteria were as follows: age ≥ 18 years; histological diagnosis of primary HER2-positive BC; newly-diagnosed LM according to LANO criteria; KPS ≥60 at the time of diagnosis of LM; coexistence of BM that have or not received WBRT or radiosurgery; systemic disease with a life expectancy of at least 3 months; concomitant drugs, including capecitabine, trastuzumab, TDM-1, pertuzumab, and hormone therapy were allowed, with the exclusion of lapatinib or other investigational agents. Neratinib was administered 240 mg daily continuously. The primary endpoint was the OS after the diagnosis of LM. Secondary endpoints were progression-free survival (PFS) following the diagnosis of LM, neurological benefit, radiological response rate, and tolerability. RESULTS From January 2018 to April 2021, 9 patients with LM have been enrolled. Median age at the time of diagnosis of LM was 44 years (95%CI 36–59) with a median KPS of 80 (95%CI 60–90). Median time since LM onset from the diagnosis of primary BC was 42 months (95%CI 11–166), and patients underwent a median number of adjuvant treatments before LM of 3 (95%CI 2–5). Three patients developed LM alone, and other 6 had LM associated with multiple brain metastases. Six-months and 1-year OS were 66.7% and 22.3%, respectively, with a median OS of 8 months (95%CI 3–13*). Median PFS was 3.5 months (95%CI 2–6) after the start of treatment. A neurological improvement was reported in 2/9 patients (22.2%), while in other 4/9 patients (44.5%) was achieved a neurological stabilization lasting for a median time of 5 months (95%CI 2–19). The best radiological response was a stable disease in 5/9 patients (55.6%), while no complete or partial response were achieved according to LANO and RANO criteria, respectively. A CSF clearance was observed in 1 patient only (11.1%) following two months of neratinib. Grade III-IV adverse events were not reported, and 2 patients only (22.2%) had mild diarrhea correlated with neratinib. CONCLUSION This is the first study that shows that neratinib might be a safe and effective treatment in LM from heavily pretreated HER2-positive BC.

Daratumumab-based combination therapies (DCT) in heavily-pretreated patients (pts) with relapsed and/or refractory multiple myeloma (RRMM).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8038-8038 ◽  
Author(s):  
Arjun Lakshman ◽  
Jithma P. Abeykoon ◽  
Shaji Kumar ◽  
S.Vincent Rajkumar ◽  
Taxiarchis Kourelis ◽  
...  
Keyword(s):  
Median Time ◽  
Progression Free Survival ◽  
Median Number ◽  
Routine Practice ◽  
Combination Therapies ◽  
First Response ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Infusion Reactions ◽  
Grade 3

8038 Background: Daratumumab-based Combination Therapies (DCT) with bortezomib (V)/ lenalidomide (R)/ pomalidomide (P) and dexamethasone (d) showed exceptional activity in RRMM in trials. Experience outside of trials since the approval of Daratumumab (D) in 2015 is limited. Methods: RRMM pts seen at Mayo Clinic, MN from 12/2015 -12/2016 were reviewed. Pts who received ≥ 1cycle of DCT were included. Time-to-event analyses were done from date of starting DCT. Common terminology criteria for adverse events v4.0 were used to grade toxicities. Results: Of 130 pts, 59% were males and median age at DCT initiation was 67 (43-93) years, ECOG performance score was ≥2 in 29%. Pts were classified as mSMART high (22%), intermediate (22%) or standard (56%) risk. Median time from diagnosis to initiation of DCT was 51.3 (5-156) months (m), and median number of prior therapies was 4 (1-14). 14% of pts were refractory to prior D monotherapy. Fifty-three (41%), 34 (26%) and 25 (19%) received DPd, DRd and DVd respectively. Eighteen (14%) pts received ‘other’ DCT. Median time to first response (≥ PR) was 3.1 m (95% CI 2.1-4.6). Overall response rate was 46%, [CR-2%, VGPR-18%, PR-26%]. Minimal response was seen in 17%, with clinical benefit rate of 62%. Median estimated follow up from initiation of DCT was 5.5 m (CI 4.2-6.1). The median duration of response was 6.1 m [CI 5.1- not reached (NR)]. Median progression free survival (PFS) was 5.5 m (CI 4.1-7.8) and median time to next therapy (TTNT) was 5.9 m (CI 4.6-9.4). Median PFS for DPd, DRd, DVd and other DCTs were 4.6 (CI 2.7-NR), 7.8 (CI 5-NR), 3.9 (CI 2.1-NR) and 3.9 (CI 2.8-8.2) m, respectively (p = 0.3). Median PFS for quadruple refractory (n = 28) MM was 2.8 m (CI 2.2-5.3) vs 5.9 m (CI 4.9-NR) for the rest (p < 0.01). Median overall survival (OS) from DCT was NR (CI 11.4-NR). Grade 3 or higher hematological toxicities were seen in 42% of pts. Other toxicities included infections (37%), fatigue (31%), infusion reactions (16%) and diarrhea (10%). Conclusions: DCT are effective in RRMM, but the PFS remains short particularly in quadruple refractory pts, reflecting the challenges encountered in managing heavily-pretreated, and often less fit patients, in routine practice.

scholarly journals Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population

2011 ◽  
Vol 165 (2) ◽  
pp. 315-322 ◽  
Author(s):  
Merina Ahmed ◽  
Yolanda Barbachano ◽  
Angela Riddell ◽  
Jen Hickey ◽  
Katie L Newbold ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Differentiated Thyroid Carcinoma ◽  
Free Survival ◽  
Hand Foot Syndrome ◽  
Secondary Endpoints ◽  
Radiological Response ◽  
Dose Reductions

AimTo evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma.MethodsPatients with progressive locally advanced/metastatic medullary thyroid carcinoma (MTC), or differentiated thyroid carcinoma (DTC) with non-radioiodine-avid disease, were treated with sorafenib 400 mg twice daily until disease progression. The primary endpoint was the radiological response rate (RR) at 6 months. Secondary endpoints were RR at 3, 9 and 12 months, biochemical responses, toxicity, biomarker analyses and progression free and overall survival (OS).ResultsA total of 34 patients were recruited to the study (15 medullary and 19 differentiated). After 6 months, the RR rate was 15% and a further 74% of patients achieved stable disease in the first 6 months. After 12 months of treatment, the RR was 21%. In the MTC patients, the RR at 12 months was 25% and OS was 100%. In DTC patients corresponding rates were 18 and 79% respectively. Median overall and progression-free survival points were not reached at 19 months. Commonest adverse events included hand–foot syndrome, other skin toxicities, diarrhoea and alopecia. Dose reduction was required in 79% patients. Median time on treatment was 16.5 months.ConclusionThis study demonstrates that sorafenib is tolerable at reduced doses over prolonged periods of time in patients with thyroid cancer. Sorafenib leads to radiological and biochemical stabilisation of disease in the majority of these patients despite dose reductions.

Weekly Cyclophosphamide and Alternate Day Prednisone: An Effective, Convenient and Well Tolerated Treatment for Relapsed Multiple Myeloma Following Autologous Stem Cell Transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4917-4917
Author(s):  
A. Keith Stewart ◽  
Young Trieu ◽  
Suzanne Trudel ◽  
Greg Pond ◽  
Joseph Mikhael ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Time ◽  
Stem Cell Transplant ◽  
Alkylating Agents ◽  
Progression Free Survival ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Protein Reduction

Abstract Alkylating agents remain among the most potent therapies available for treatment of Multiple Myeloma (MM). Their use prior to, or following, autologous stem cell transplant (ASCT) is, however, compromised by concerns about stem cell quality and by myelosuppression limiting effective dose delivered. To address this concern we have studied a combination of cyclophosphamide 500 mg p.o. once weekly and prednisone 100 mg p.o. on alternate days in 66 patients requiring salvage therapy post-ASCT. Dose reductions were allowed for toxicity beginning at cycle 2. On an intent to treat basis, 66 patients received this regimen, however, 7 of these patients were not fully evaluable for response due to non-secretory disease. Of the 59 patients evaluable for response, the median time from transplant to treatment was 26.4 months (range, 6.0 to 66.6). The median time from post-transplant relapse to start of cyclophosphamide and prednisone (C/P) therapy was 1.4 months. The median number of therapies from time of diagnosis to C/P initiation was 2 (range, 1.0 to 5.0). At the date of analysis, treatment with C/P is ongoing in 12 (20.3%) patients, with a median duration of 3.6 months (range, 1.9 to 11.6). The 47 patients who have completed C/P therapy were treated for a median time of 5.5 months (range, 0.5 to 21.7). The reason for discontinuation among these 47 patients included disease progression (42.6% of patients discontinued), plateau disease (21.3%), receiving a second transplant (17.0%), toxicity (10.6%), or switched to another regimen (8.5%). A partial response (&gt;50% protein reduction) was obtained in 37.3% of patients, 18.6% attained minimal response (25–50% protein reduction), 33.8% patients stable disease, while 10.2% patients had progressed on treatment. The estimated median (95% CI) months of progression-free survival after start of C/P treatment is 14.9 (8.7, 21.7). Twenty-three (38.9%) of patients have relapsed after C/P treatment, a median (range) of 8.7 (0.5–65.7) months after start of C/P treatment. At 6 months 74.3% (95% C.I. 61.9% – 89.1%) of patients were progression-free with 28% (95% CI: 16.1–49.2%) progression free at two years. At time of analysis, 44 (74.6%) patients are still alive, with a median follow up of 10.6 months (range, 1.2 to 65.7) since the start of C/P therapy. Fifteen patients have died at a median 13.0 months (range, 1.4 to 61.7) since the time of C/P initiation. The median overall survival (95% C.I.) is estimated to be 35.9 months (24.2, NA). These results demonstrate that the combination of oral cyclophosphamide and prednisone is an effective (56% MR or PR), very well tolerated (10% discontinued due to toxicity) and convenient treatment as salvage MM therapy post-ASCT. The relative lack of myelosuppression allows for re-collection of stem cells and salvage transplant while retaining other active second line agents for later relapse. This regimen thus compares favorably with recent salvage therapeutics introduced in MM and is now being studied in combination with these newer active agents and in induction therapy.

High Dose Zevalin (90Yttrium Ibritumomab Tiuxetan) Treatment with PBSC Support in Refractory-Resistant NHL Patients: Preliminary Results of a Phase I/II Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 488-488 ◽  
Author(s):  
Anna Vanazzi ◽  
Pierfrancesco Ferrucci ◽  
Mahila Ferrari ◽  
Liliana Calabrese ◽  
Marta Cremonesi ◽  
...  
Keyword(s):  
Phase I ◽  
Median Time ◽  
Dose Intensity ◽  
Median Number ◽  
Therapeutic Options ◽  
Clinical Activity ◽  
High Dose ◽  
Resistant Refractory ◽  
Duration Of Response ◽  
Heavily Pretreated

Abstract Therapeutic options are limited for resistant-refractory high-grade NHL pts not suitable to HDCT or for those pts relapsing after ABMT. Zevalin has been already demonstrated active in elderly pts with resistant-primary refractory DLBCL at dose of 0.4 mCi/kg, however duration of response is short. Increasing RIT dose intensity might improve efficacy. There are no data about the use of Zevalin at myeloablative dosage. We present feasibility and toxicity results of a phase I/II study of HD-Zevalin with PBSC support in resistant-refractory NHL pts. Three Zevalin dose-levels were fixed: 0.8, 1.2, 1.5 mCi/kg; from April 2004 to July 2005 12pts were enrolled, 4pts at each dose level. Median age was 66,5 ys (28–73), 83% male. All pts had stage III/IV at diagnosis; 7DLBCL; 3MCL, 1FL, 1transformed MZL. 7pts had received more than 3 previous CT regimens. All pts had received prior rituximab, 3pts RT, 6pts HD-CT. BM was negative in all pts before RIT. 1Week prior to Zevalin all pts underwent dosimetry and if no abnormal uptake was observed they received the planned dose. On Day −7 and 0 imaging and therapeutic doses were preceded by rituximab 250mg/mq. On Day13 pts were reinfused with PBSC previously harvested. On Day28 from reinfusion engraftment was considered to be delayed if WBC/ANC were&lt;1.0x109/L or PLT&lt;20x109/L. All pts engrafted promptly after PBSCT with median time to WBC/ANC&gt;1.0x109/L and PLT&gt;20x109/L of 19 (range 0–23) and 12 days (0–22) from PBSCT. PLT and ANC count nadirs were observed at 21 (0–24) and 25 (0–31) days after Zevalin with median values of 11x109/L(4–35) and 0.24x109/L(0.01–1.09). Median time to recovery from nadir was 16,5 days (4–175) for PLT and 17days (7–175) for ANC. 8pts required PLT transfusions, 4pts RBC transfusions; median number of PLT transfusions:1(1–4). No G-CSF was administered. No significant differences in terms of haematologic toxicity were observed among the 3 levels. No pulmonary, renal or cardiac toxicity was observed. 11/12 pts are now evaluable for response: 5pts experienced a CR (2 at 0.8mCi/kg, 2 at 1.2mCi/kg, 1 at 1.5mCi/kg), 1 pt receiving 1.5 mCi/kg a PR (ORR 50%); to date 4 pts maintain CR at 12, 11, 9 and 8 months after treatment. Conclusion: Zevalin at dosage higher than MTD is feasible with PBSC support. Even at dosage 4 times higher than standard, HD-Zevalin could be safely delivered in elderly and heavily pretreated pts, including those who previously received HD-CT. Clinical activity and mild treatment-related toxicities suggest that HD-Zevalin is an interesting modality treatment to be further investigated as an alternative therapeutic options for resistant-refractory NHL.

Bortezomib and Dexamethasone as Maintenance therapy in Relapse/Refractory multiple myeloma Patients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2771-2771 ◽  
Author(s):  
Giulia Benevolo ◽  
Alessandra Larocca ◽  
Patrizia Pregno ◽  
Francesca Gay ◽  
Barbara Botto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Median Time ◽  
Salvage Therapy ◽  
Univariate Analysis ◽  
Single Agent ◽  
Haemoglobin Concentration ◽  
Progression Free Survival ◽  
Median Number

Abstract Background: Despite the advances in the treatment for multiple myeloma (MM) in the past decade, it still remains an incurable haematological disease and the majority of patients still experience relapse. Bortezomib is a novel proteasome inhibitor approved for the treatment of MM patients. Several studies have demonstrated its efficacy as front-line therapy and in relapsed, advanced MM but no data are available as maintenance therapy (MT) in refractory/relapsed MM. Patients and methods: The aim of this study is to evaluate the safety and the efficacy of bortezomib/dexamethasone MT (1.3 mg/mq bortezomib on days 1 and 15; 20 mg dexamethasone on days 1–2 and 15–16 in a 28-day cycle for a total of 6 cycles) in patients with refractory/relapse MM who responded to salvage therapy. Results: From October 2004 until April 2008, 40 MM patients have been enrolled. The characteristics of the patients were as follows: 20 males and 20 females, median age was 70 years (IQR:66–75). Median haemoglobin value was 10.85 (IQR:10.175–12.225) and 7 (18%) patients had a renal failure. Skeletal disease was present in 27 (68%) patients. The median number of prior therapies was 2 (1–4). The salvage therapy included bortezomib as single agent or in combination with steroids and/or thalidomide in 12 patients (30%). Median time from diagnosis to the first dose of MT was 41 months (IQR:26–59). The median number of bortezomib infusion was 8 (1–18). After a median follow up of 13 months (IQR:6–31), 10 patients died for PD and 4 patients for infections. The MT improved the quality of response and converted in 1 CR and 4 VGPR the PR after salvage therapy in 5 patients; moreover, we observed a remarkable decreased of M component in 11 patients. The median time to progression was 23 months (95%CI: 8-not reached) with a progression free-survival at 1 year of 69% (95%CI: 50–82). The overall survival at 1 years was 63% and the cumulative incidence of death due to PD adjusted for competitive risk event was 25% (95%IC:10–41). In a univariate analysis the response rate to MT was not significantly affected by age, sex, number or type of previous therapy and haemoglobin concentration. Non-dose-limiting toxicities included neuropathy grade 1 (12 pts), herpes zoster reactivation (2 pts) and gastrointestinal affections (1 pts). Conclusion: The combination bortezomib/dexamethasone can be safely administered as a maintenance therapy in relapse/refractoy MM. These preliminary data suggest that bortezomib/dexametasone MT can improve remission duration and also quality of response with an acceptable toxicity.

A phase II trial of salvage treatment with gemcitabine and S-1 combination in heavily pretreated patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3595-3595
Author(s):  
Sun Jin Sym ◽  
Junshik Hong ◽  
Hee Kyung Ahn ◽  
Jinny Park ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Median Number ◽  
Heavily Pretreated

3595 Background: We conducted a phase II trial of gemcitabine with S-1 to evaluate the activity and toxicity of such a combination in heavily pre-treated patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after treatment with fluoropyrimidines-, oxaliplatin- and irinotecan-containing regimens. Methods: 36 pts were enrolled, with the following characteristics: 19 females (53%), median age 57 (28-72), 30 EOGO PS 0-1 (83%). S-1 was given orally (30 mg/m2) b.i.d for 14 consecutive days and gemcitabine (1000 mg/m2) was given on days 1 and 8, every 21 days, until disease progression and for a maximum of 9 cycles. The primary endpoint was objective response rate (ORR). Results: The median number of cycles was 5 (range 1-9), ORR was 16.7% (95% confidence interval [CI] 4.5-28.9%) and disease control rate was 61.1% (95% CI 45.2-77.0%) with 6 partial responses and 16 stable diseases. Median duration of disease control was 5.8 months (95% CI 4.1-7.5 months). Median progression-free survival was 3.7 months (95% CI 2.2-5.2 months) and median overall survival was 10.0 months (95% CI 7.4-12.7 months). Grade 3-4 toxicities were rare (neutropenia 12%, anemia 11%, leucopenia 6%, thrombocytopenia 3% and diarrhea 3%). Conclusions: Combination chemotherapy with gemcitabine and S-1 was a convenient, well tolerated and efficacious for heavily pre-treated pts with mCRC. This regimen warrants further evaluation in pts with good PS but no further treatment options.

Efficacy analyses of a randomized phase III clinical trial of combined therapy with CPT-11/CDDP versus CPT-11 alone in patients with advanced or recurrent gastric cancer refractory to prior S-1 chemotherapy.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 69-69
Author(s):  
Hitoshi Inagaki ◽  
Kazuhiro Nishikawa ◽  
Kazumasa Fujitani ◽  
Naotoshi Sugimoto ◽  
Tadashi Shigematsu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Combined Therapy ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Second Line ◽  
Eligibility Criteria ◽  
Recurrent Gastric Cancer ◽  
Secondary Endpoints

69 Background: There has been no established regimen as the second-line treatment for advanced gastric cancer (AGC), though CPT-11 showed survival benefit over BSC. Combination of CPT-11 with CDDP is one of the promising regimens as the second-line chemotherapy after S-1 mono-therapy. Methods: This is a prospective, multicenter randomized phase III study comparing CPT-11+CDDP (Arm A) vs. CPT-11 alone (Arm B) in patients with advanced or recurrent gastric cancer resistant to S-1 mono-therapy or prior adjuvant chemotherapy using S-1. Eligibility criteria include histologically confirmed gastric adenocarcinoma, age over 20 years old, PS: 0-2, adequate organ functions and written informed consent. Arm A: patients received CPT 11 60mg/m2 and CDDP 30mg/m2 on day 1, q2w. Arm B: patients received CPT-11 150mg/m2on day 1, q2w. Stratification was made according to PS, advanced or recurrence cases, institution and presence or absence of measurable target lesions. Primary endpoint was overall survival (OS), secondary endpoints were progression free survival (PFS), time to treatment failure (TTF), response rate (RR), and safety. Results: 168 patients were registered between 2007 and 2011. Arm A (n=84) and Arm B (n=84) were well balanced for baseline factors. Median age was 67 vs 68 years old, number of advanced/recurrence after resection was 36/48 vs 35/49, and median number of treatment course was 5 vs. 6 (range:0-31, 0-39). Common grade 3/4 toxicities in Arm A vs. Arm B were neutropenia; 35.4% vs. 27.2% (p=0.259), anemia; 15.9% vs. 3.7% (p=0.009), diarrhea; 0% vs. 2.5% (p=0.152), nausea; 3.7% vs. 4.9% (p=0.687), vomiting; 1.2% vs. 3.7% (p=0.305), anorexia 6.1% vs. 8.6% (p=0.534). The rate of patients who were required dose modification for these toxicities was 22.9% vs 21.4%. The pooled OS, PFS and RR for both Arms were as follows; 13.8 months (95% CI, 10.7 to 17.5), 4.5 months (95% CI, 3.7 to 5.1), and 13.7%. Conclusions: There was no significantly difference in the incidence and severity of adverse events in both Arms except for anemia. Updated efficacy data of secondary endpoints will be presented. Clinical trial information: UMIN000002571.

A phase II trial of metformin and fluorouracil (MetFU) for patients (pts) with metastatic colorectal cancer (mCRC) refractory to standard treatment.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 601-601 ◽  
Author(s):  
Vanessa Costa Miranda ◽  
Luiza Dib Faria ◽  
Maria Ignez Freitas Melro Braghiroli ◽  
Monica Jacobs ◽  
Jorge Sabbaga ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Free Survival ◽  
Best Response ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
Tumor Types

601 Background: Pts with mCRC whose disease progressed after 5-FU, oxaliplatin, irinotecan and monoclonal antibodies have an unmet medical need. There is growing evidence suggesting an antitumoral effect of metformin in several tumor types, including CRC. Methods: Our primary objective was to evaluate the efficacy and safety of MetFU in heavily pretreated CRC pts with current progressive disease Last dose of 5-FU was administred at least 4 months prior to enrollment. Efficacy was defined as disease control rate at 8 weeks, using RECIST 1.1. Secondary endpoints were progression free survival, overall survival and tolerability. Single-arm Simon two-stage phase II trial was used. The treatment consisted of metformin 850 mg bid continuously plus 5-FU 425mg/m2 + Leucovorin (LV) 50 mg weekly for 4 weeks until disease progression, unacceptable toxicity or consent withdrawn in pts with mCRC who had progressed to conventional lines of treatment. Results: In the first stage, 22 pts were included: 12 pts (54%) were men, median age was 55 years and 59% were classified as an ECOG 1.14 pts faced treatment adverse events and 4 pts were excluded due to toxicity G3/4 - 2 pts had thrombocytopenia and 2 had limiting fatigue. Median time on treatment was 3.8 months, and 17 pts were evaluable for response: 6 pts (27%) had stable disease at 8 weeks as best response, with a median progression free survival (PFS) of 8.1 months. For the whole cohort, median overall survival was 5.6 months (IC95%: 3.1-8.2) and PFS was 2.0 months (IC95%: 1.8-2.3). Conclusions: Our results suggest that metformin may have antitumor activity when combined with 5-FU/LV in a subgroup of mCRC pts, with acceptable toxicity. It is unlikely that 5-FU alone had activity in these heavily treated pts. Clinical trial information: NCT01941953.

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