NGR-hTNF and doxorubicin in relapsed ovarian cancer (OC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5059-5059
Author(s):  
Domenica Lorusso ◽  
Giovanni Scambia ◽  
Giulia Amadio ◽  
Alessia di Legge ◽  
Antonella Pietragalla ◽  
...  
Keyword(s):  
Median Duration ◽  
Human Tumor ◽  
Progression Free Survival ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Grade 3 ◽  
Necrosis Factor

5059 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to promote antitumor immune responses and to improve the intratumoral doxorubicin (D) uptake by selectively damaging tumor vessels. Methods: OC patients (pts) with progressive disease (PD) after ≥ 1 platinum/taxane regimen and with a platinum free interval lower than 6 months (PFI <6) or ranging from 6 to 12 months (PFI 6-12) received NGR-hTNF (N) 0.8 µg/m2 and D 60 mg/m2 on day 1 every 3 weeks. Primary endpoint of this phase 2 trial was response rate by RECIST criteria with a target of ≥ 6/37 responding pts. Secondary aims were progression free survival (PFS) and overall survival (OS). Results: 37 pts (median age 57 years; PS 0/1 32/5; PFI < 6/6-12 25/12; prior regimens 1-5) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6/mL (interquartile range 1.2-2.1). In all, 177 cycles were given, with 18 pts (49%) receiving ≥ 6 cycles and 12 pts (32%) 8 cycles. Neither grade 3/4 adverse events (AEs) related to N nor increase of D-related AEs were noted. Common grade 1/2 AEs included chills (65%). Eight pts (23%; 95% CI 12-39) had partial response (PR; 2 with PFI < 6 and 6 with PFI 6-12; median duration: 8.2 months). Fifteen pts had stable disease (SD, 43%; 10 with PFI < 6 and 5 with PFI 6-12; median duration: 4.9 months) for an overall disease control (DC, PR+SD) rate of 66%. Mean changes from baseline in target tumor size after 2, 4, 6, and 8 cycles were 2%, -54%, -69%, and -77%, respectively. Median PFS was 5.0 months (95% CI 3.1-6.9) and median OS was 17.0 months (10.4-23.6). In pts with PFI < 6 or 6-12, median PFS were 3.8 and 7.8 months (p=.03) and median OS were 14.3 and 20.1 months (p=.14), respectively. Pts with DC had longer median OS than those with early PD (24.0 and 4.9 months, respectively, p=.02). Longer PFI (p=.03) and higher PBLC (p=.01) were associated with better PFS, while OS correlated only with PBLC (p=.001). In the subset with PFI < 6, pts with PBLC ≥ or < 1.2/mL (1st quartile) had median PFS of 4.9 and 2.6 months (p=.02) and median OS of 15.8 and 4.3 months (p=.0001), respectivel Conclusions: A randomized phase II trial is currently testing D ± NGR-hTNF in pts with PFI < 6 (refractory/resistant). The role of PBLC as blood-based biomarker deserves further investigation.

NGR-hTNF and doxorubicin in relapsed small-cell lung cancer (SCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7085-7085 ◽  
Author(s):  
Raffaele Cavina ◽  
Vanesa Gregorc ◽  
Silvia Novello ◽  
Francesco Grossi ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Phase Ii ◽  
Median Duration ◽  
Human Tumor ◽  
Progression Free Survival ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Resistant ◽  
Grade 3 ◽  
Further Development ◽  
Necrosis Factor

7085 Background: By selectively damaging tumor vasculature, NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to improve intratumoral uptake of doxorubicin (D). A phase I trial selected NGR-hTNF 0.8 µg/m2/day(d)1 and D 75 mg/m2/d1 every 3 weeks (q3w) for phase II. Methods: SCLC pts failing one or more platinum-based regimen received NGR-hTNF until progressive disease (PD) and D up to 550 mg/m2. This phase II trial (n=27 pts) had progression-free survival (PFS) as primary end point, with tumor response assessed q6w by RECIST, while secondary end points included adverse events (AEs), disease control rate (DCR), and overall survival (OS). Results: Among 28 pts enrolled (median age 63 years; M/F 19/9; PS 0/1-2 13/15; prior lines 1/2-3 20/8), 16 pts had platinum-resistant (R) disease (PD≤3 months) and 12 pts platinum-sensitive (S) disease (PD>3 months). At baseline, median neutrophil to lymphocyte ratio (NLR) was 4 (range 1-20). A total of 114 cycles were given (range 1-10), with 13 pts (46%) having ≥ 4 cycles and 9 pts (32%) ≥ 6 cycles. No grade 3/4 AEs related to NGR-hTNF were noted, while grade 1/2 AEs were transient chills (61%). NGR-hTNF did not apparently increase D-related AEs. Median PFS was 3.2 months (95% CI 2.6-3.8) and 1-year OS rate was 34%. Overall, DCR was 55% (95% CI 35-74), comprising 6 partial responses (22%; median duration: 6.3 months) and 9 stable diseases (33%; median duration: 4.1 months). Mean changes from baseline in target tumor size after 2, 4, and 6 cycles were -9%, -29%, and -32%, respectively for R disease and -11%, -20%, and -43%, respectively for S disease. In pts pretreated with ≥ 2 lines, DCR was 75%, median PFS was 5.1 months, and 1-year OS rate was 44%. In pts with R or S disease, DCR were 50% and 58% (p=.72), median PFS were 2.7 and 4.1 months (p=.07), and 1-year OS rates were 27% and 42% (p=.65), respectively. At multivariate analyses, PFS was not related to baseline characteristics, while an improved OS was associated only with a low NLR. The 1-year OS rate was 48% in pts with NLR ≤ 4 and 10% in pts with NLR > 4 (p=.007), while in pts with NLR ≤ 4, 1-year OS rate was 46% in R disease and 50% in S disease. Conclusions: This combination is well tolerated and active in platinum resistant and sensitive SCLC and further development is of interest.

scholarly journals ACTR-24. A RANDOMIZED PHASE II TRIAL OF VELIPARIB (V), RADIOTHERAPY (RT) AND TEMOZOLOMIDE (TMZ) IN PATIENTS (PTS) WITH UNMETHYLATED MGMT (uMGMT) GLIOBLASTOMA (GBM): THE VERTU STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi18-vi18 ◽  
Author(s):  
Mustafa Khasraw ◽  
Kerrie Leanne McDonald ◽  
Mark Rosenthal ◽  
Zarnie Lwin ◽  
David Ashley ◽  
...  
Keyword(s):  
De Novo ◽  
Performance Status ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Randomized Phase Ii ◽  
Common Grade ◽  
Grade 3

Abstract BACKGROUND TMZ offers minimal benefit in pts with de novo uMGMT GBM. V is synergistic with RT and TMZ in uMGMT preclinical GBM models, safe when combined with either RT or TMZ clinically, but the triplet (V+RT+TMZ) is poorly tolerated. VERTU tested V in pts with uMGMT GBM. METHODS VERTU is a randomized Phase 2 trial comparing Standard Arm (Arm A), RT (60Gy/30 fractions) + TMZ (75mg/m2 daily) followed by TMZ (150–200mg/m2D 1–5) every 28 days for 6 cycles vs Experimental Arm (Arm B), RT (60Gy/30 fractions) + V (200mg PO BID) followed by TMZ (150–200mg/m2D 1–5) + V (40mg bid, D 1–7) every 28 days for 6 cycles in pts with de novo uMGMT GBM according to centralised testing. RESULTS 125 pts were randomized 1:2 (41:84). The 2 groups were matched for age, sex, performance status and extent of resection. Median follow-up was 25.8 months and 91 pts had died. The 6-month Progression-Free Survival (6mPFS) for Arms A and B were 34% (95% CI 20–48) and 46% (95% CI 36–57) respectively. The median PFS for Arms A and B were 4.2m (95% CI 2.5–6.0) and 5.7m (95% CI 4.1–6.6) respectively (HR = 0.80, 95%CI 0.55–1.18). 55% of pts in both arms experienced Grade 3/4 adverse events (AEs) with no significant differences in frequency or severity between the arms. Most common Grade 3/4 AEs were thrombocytopenia, seizures, hyperglycaemia and diarrhoea. CONCLUSION VERTU demonstrated that a novel treatment strategy for patients with de novo uMGMT GBM was feasible and tolerable. The observed 6mPFS and PFS were similar in both arms. Overall survival and other endpoints will be presented. Central MRI review, biomarker analyses, including DNA repair and methylation signature analyses are ongoing. (ANZCTR#ACTRN12615000407594).

Updated survival results of the randomized phase II study comparing cisplatin/capecitabine (CX) with epirubicin plus CX (ECX) in advanced gastric cancer (AGC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 46-46 ◽  
Author(s):  
T. Lim ◽  
J. Yun ◽  
J. Lee ◽  
S. Park ◽  
J. Park ◽  
...  
Keyword(s):  
Performance Status ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
To Receive ◽  
Line Chemotherapy

46 Background: We previously reported results of a randomized study showing that CX is equally active to ECX in terms of progression-free survival (PFS) (Yun et al. Eur J Cancer. 2010). Here we report updated overall survival (OS) results with an additional 12 months' follow-up. Methods: Ninety-one chemotherapy-naïve patients with histologically-confirmed, measurable AGC were randomized to receive CX (cisplatin 75 mg/m2 iv on day 1 and capecitabine 1,000 mg/m2 bid po on days 1-14, n=45) or ECX (epirubicin 50 mg/m2 plus CX, n=44) every 3 weeks. After CX or ECX had failed, second-line chemotherapy (SLC) was recommended for all patients if their performance status was preserved. Results: Treatment duration was similar for both arms (4.4 for CX v 4.2 months for ECX). There was no relevant difference in the occurrence of overall grade 3 or 4 toxicities between the CX and ECX arms (80% v 78%, respectively; p=0.516). However, none in the CX and 12% in the ECX arm discontinued treatment because of toxicity. There were no significant differences in therapeutic efficacy between CX and ECX with respect to the response rate (38% v 37%, respectively), PFS (6.4 v 6.5 months), as well as OS (12.7 v 13.8 months; p=0.51). After failure, 60% of patients (26 CX and 28 ECX patients) received SLC. However, OS was not differed whether a patient was treated with SLC or not (13.1 v 11.2 months; p=0.94). Conclusions: The present analysis confirms previous findings that both CX and ECX appear to be comparatively active as first-line chemotherapy for AGC. Furthermore, the role of SLC in AGC warrants further evaluation. No significant financial relationships to disclose.

NGR-hTNF plus chemotherapy as first-line therapy of non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7581-7581
Author(s):  
Vanesa Gregorc ◽  
Nicoletta Zilembo ◽  
Francesco Grossi ◽  
Tommaso M De Pas ◽  
Gilda Rossoni ◽  
...  
Keyword(s):  
Human Tumor ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line Therapy ◽  
Phase 2 Trial ◽  
Younger Age ◽  
Common Grade ◽  
Study Population ◽  
Grade 3 ◽  
Nsclc Patients

7581 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is a selective vascular targeting agent able to improve intratumoral chemotherapy uptake. Methods: Chemo-naive, stage IIIb-IV NSCLC patients (pts), stratified by histology (nonsquamous or squamous) and PS (0 or 1), were randomized to cisplatin 80 mg/m2/day(d)1 plus either pemetrexed 500 mg/m2/d1 (nonsquamous) or gemcitabine 1,250 mg/m2/d1+8 (squamous) every 3 weeks (q3w) up to 6 cycles with (arm A) or without (arm B) NGR-hTNF 0.8 μg/m2/d1 q3w until progression. Progression free survival (PFS) was primary end point of this phase 2 trial (β=20%, α=20%, HR=0.62, and n=102). Secondary end points included adverse events (AEs), response rate (RR) and overall survival (OS). Results: 59 pts were assigned to arm A and 57 to arm B. Baseline characteristics in arm A/B were: median age 62/63; male 34/37; PS 1 21/21; squamous 15/15; nonsmokers 14/12; EGFR mutations 5/5. For the nonsquamous group, 281 cycles (mean 6.5; range 1-18) were given in arm A and 190 (mean 4.7; range 1-6) in arm B, while for the squamous group, 88 (mean 6.3; range 1-19) in arm A and 48 (mean 3.7; range 1-6) in arm B. Most common grade 3/4 AEs were neutropenia 14% vs 17% and fatigue 7% vs 11% in arm A and B, respectively. No grade 3/4 AEs related to NGR-hTNF or bleeding in pts with squamous histology were noted. Median follow-up was 12.4 months. In the whole study population, median (m)PFS was 5.8 vs 5.7 months (HR=0.95), RR was 23% vs 19%, and 1-year OS was 62% vs 62% in arm A and B, respectively. In the nonsquamous subset, a trend toward longer mPFS in arm A compared to arm B was noted in pts with a PS of 1 (6.7 vs 4.6 months, respectively), nonsmoking history (6.2 vs 3.4), younger age (6.5 vs 3.4), and EGFR mutations (7.2 vs 3.3). In the squamous subset, mPFS was 5.1 vs 3.9 months (HR=0.71) and mOS was 14.2 vs 10.8 months (HR=0.73) in arm A and B, respectively. In these pts, ORR was 36% in arm A and 23% in arm B, while median changes from baseline in target tumor size after 2, 4, and 6 cycles were -29%, -45%, and -41%, respectively in arm A, and -18%, -22%, and -14%, respectively in arm B. Conclusions: Regardless of histology, NGR-hTNF can be safely given with standard chemotherapy, showing tolerability and hint of activity in squamous NSCLC.

Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis

Chemotherapy ◽  
2021 ◽  
pp. 1-7
Author(s):  
Kotone Hayuka ◽  
Hiroyuki Okuyama ◽  
Akitsu Murakami ◽  
Yoshihiro Okita ◽  
Takamasa Nishiuchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Unresectable Pancreatic Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Common Grade ◽  
Grade 3

<b><i>Introduction:</i></b> Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. <b><i>Methods:</i></b> Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. <b><i>Results:</i></b> The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). <b><i>Conclusions:</i></b> GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.

Lonsurf (trifluridine/tipiracil): Assessing the impact of dose related toxicities and progression free survival in (refractory) metastatic colorectal cancer

2021 ◽  
pp. 107815522110179
Author(s):  
Olivia R Court
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Dose Reduction ◽  
Progression Free Survival ◽  
Electronic Patient Records ◽  
Free Survival ◽  
Length Of Treatment ◽  
Common Grade ◽  
Grade 3 ◽  
The Impact

In the RECOURSE trial which lead to its accreditation, Lonsurf (trifluridine/tipiracil) was shown to extend progression free survival (PFS) by 1.8 months in metastatic colorectal cancer. This Trust audit aims to assess the average quantity of cycles of Lonsurf received by participants and the length of time it extends PFS. Similarly, to identify how many participants required a dose-reduction or experienced toxicities which necessitated supportive therapies. Quantitative data was collected retrospectively from all participants who had received ≥1 cycle of Lonsurf from The Clatterbridge Cancer Centre (CCC) from 2016 until June 2020. Participant electronic patient records were accessed to identify toxicity grading, length of treatment received, the date progression was identified, if dose reductions were applied and if supportive therapies were administered. Lonsurf extends PFS in patients with metastatic colorectal cancer at CCC by 3.0 months (95% CI: 2.73–3.27) and average treatment length was 2.4 months. However, 78 participants (41.5%) received a dose reduction due to toxicities. A total of 955 toxicities were recorded by participants; the most commonly reported toxicities irrespective of grade were fatigue (33.8%), diarrhoea (13.8%) and nausea (12.3%). The most common grade ≥3 toxicities were constipation and infection. The most frequently utilised supportive therapies were loperamide (49.6%) and domperidone (49.1%). Granulocyte colony stimulating factor (GCSF) was required by patients on 5 occasions (0.3%) in total. Lonsurf extends median PFS in patients with metastatic colorectal cancer by 3.0 months. The most common grade ≥3 toxicities which necessitated supportive therapies or a dose reduction were gastrointestinal and infection.

scholarly journals PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression

2021 ◽  
Author(s):  
Jonathan Weller ◽  
Sophie Katzendobler ◽  
Philipp Karschnia ◽  
Stefanie Lietke ◽  
Rupert Egensperger ◽  
...  
Keyword(s):  
Stereotactic Biopsy ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Who Grade ◽  
Free Survival ◽  
First Relapse ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
Histological Progression

Abstract Introduction The role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy. Methods Patients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed. Results PFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS. Conclusions PCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 772-778 ◽  
Author(s):  
Paul Richardson ◽  
Sundar Jagannath ◽  
Mohamad Hussein ◽  
James Berenson ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Prior Treatment ◽  
Once Daily ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Treatment Regimens ◽  
Common Grade ◽  
Grade 3

Abstract Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351.

GEIS 39: Phase II trial of nabpaclitaxel for the treatment of patient with multiply relapsed/refractory desmoplastic small round cell tumor (DSRCT) and Ewing sarcoma (EwS).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11529-11529
Author(s):  
Jaume Mora ◽  
Mariona Suñol ◽  
Nadia Hindi ◽  
Alicia Castañeda ◽  
Andrés Redondo ◽  
...  
Keyword(s):  
Single Agent ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Pediatric Solid Tumors ◽  
Meaningful Activity ◽  
Common Grade ◽  
Central Pathology ◽  
Grade 3 ◽  
Further Development

11529 Background: Nab-paclitaxel (albumin-bound paclitaxel) has shown preclinical activity against pediatric solid tumors. Preclinical data in EwS PDX models suggested high activity of nab-paclitaxel in tumors expressing high-levels of SPARC. Tumoral SPARC facilitates the accumulation of albumin in the tumor and increases the effectiveness of albumin-bound paclitaxel. Nab-paclitaxel utilizes albumin to deliver paclitaxel via caveolin-mediated endocytosis which is expressed in the EwS cells surface. We hypothesized that SPARC can be a predictive biomarker for nab-paclitaxel in EwS and DSRCT that could potentially be relevant for a better design of clinical trials and personalized treatments using nab-paclitaxel. Methods: Main endpoint of GEIS-39 was the overall response rate (ORR) assessed by RECIST 1.1 criteria with centralized pathology and imaging review. Secondary objectives included safety according to the CTCAE 4.0 criteria. Patients aged ≥ 6 months and ≤ 40 years, with relapsed/refractory DSRCT were eligible after having received at least one previous poly-chemotherapy line; EwS must have received at least two standard chemotherapy lines. Prior taxane therapy was accepted. Central pathology review selected for tumors with > Grade 3 (intense and diffuse) expression of SPARC by immunohistochemistry to be eligible. Nab-paclitaxel was administered as follows: age ≥ 21 and ≤ 40 years: 125 mg/m2 days 1, 8 and 15 in cycles of 28 days; age ≥ 6 months and ≤ 20 years: 240 mg/m2 days 1, 8 and 15 in cycles of 28 days. A 30% ORR was anticipated with a sample size of 25 patients needed to test the hypothesis. Stopping rule was set at 1 response within the first 16 treated pts. If 5 or more successes were observed in 25 pts, the results of the trial will warrant further investigation. Results: Twenty-nine patients were enrolled from June 2017 until October 2019, 11 DSRCT and 18 EwS. Median age was 32 years (range 14-69), and 5 females and 24 males were included, having received a median of 3 previous systemic treatment lines. Patients received a median of 3 cycles of nab-paclitaxel (range 1-17). In the EwS cohort an ORR of 33.3% (all partial responses, median duration 2 months) and 16.7% of stabilizations were achieved. No objective responses were observed among DSRCT pts, but 27.3% of pts achieved a stabilization. Overall, median progression free survival was 2.8 months and median overall survival 12.1 months, with no significant differences between DSRCT and EwS cohorts. Most common grade 3 toxicities were neutropenia (20.7%) and diarrhea (10.3%). Conclusions: Single agent nab-paclitaxel in biomarker selected EwS patients, but not in DSRCT, provided clinically meaningful activity that deserves further development. Nab-paclitaxel had a manageable adverse event profile. Clinical trial information: 2016-002464-14.

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.

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