Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 204-204 ◽  
Author(s):  
Pascal Hammel ◽  
Jill Lacy ◽  
Fabienne Portales ◽  
Alberto F. Sobrero ◽  
Roberto A. Pazo Cid ◽  
...  
Keyword(s):  
Adverse Events ◽  
Progressive Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Induction Phase ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Ic Treatment

204 Background: In the phase 3 MPACT study, treatment with nab-P + G resulted in a > 3-fold reduction in primary pancreatic tumor burden vs G in patients with metastatic PC, suggesting the potential for activity against LAPC. This international, multicenter single arm, phase 2 trial (LAPACT) was designed to evaluate the efficacy and safety of an induction phase regimen of nab-P + G in previously untreated patients with LAPC. Methods: Treatment-naive patients with unresectable LAPC and Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 were enrolled. The induction phase was designed as 6 cycles of nab-P 125 mg/m2 + G 1000 mg/m2 on D 1, 8, and 15 of each 28-day cycle. After induction, patients without progressive disease or unacceptable adverse events were eligible for continued treatment with nab-P + G, chemoradiation, or surgery per investigator’s choice (IC). Surgery could occur prior to completing 6 induction cycles if the investigator deemed there had been a sufficient tumor response. The primary endpoint was time to treatment failure (TTF) in patients treated with nab-P + G as induction therapy followed by IC treatment. Key secondary endpoints included disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 107 patients enrolled, 106 were evaluable for the safety analysis. No new toxicities were identified. The most common grade ≥ 3 treatment-emergent adverse events during induction were neutropenia (42%), anemia (11%), and fatigue (10%); grade 3 peripheral neuropathy occurred in 4% of patients. The most frequent reasons for discontinuing induction were adverse events (18%) and progressive disease (7%). Forty-six (43%) patients received IC treatment after induction: 13 (12%) continued nab-P + G, 17 (16%) received chemoradiation, and 16 (15%) underwent surgical resection (R0, n = 7; R1, n = 9). DCR and ORR during induction were 78% and 35%, respectively; with a median TTF of 8.6 months and median PFS of 10.2 months. Conclusion: A nab-P + G induction regimen in LAPC appears tolerable and feasible and is associated with encouraging antitumor activity and promising TTF and PFS. NCT02301143. Clinical trial information: NCT02301143.

Washington University experience with FOLFIRINOX in pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 354-354 ◽  
Author(s):  
Parvin F. Peddi ◽  
Benjamin R. Tan ◽  
Joel Picus ◽  
Steven Sorscher ◽  
Rama Suresh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Advanced Disease ◽  
Performance Status ◽  
Locally Advanced ◽  
Published Data ◽  
Ecog Performance Status ◽  
Borderline Resectable ◽  
Locally Advanced Disease ◽  
Grade 3

354 Background: The FOLFIRINOX (5-FU, leucovorin, irinotecan, oxaliplatin) regimen has recently been shown to be an effective treatment with a significant survival benefit in patients with metastatic pancreatic cancer. Concern for treatment-related toxicity, however, has hampered the adoption of this regimen in clinical practice. A FOLFIRINOX registry was created at our institution to document FOLFIRINOX tolerability and efficacy. Methods: Patients with pancreatic cancer who had received at least one dose of FOLFIRINOX were enrolled in the registry. Demographic information, treatment dosage, adverse events, and efficacy data were obtained. Radiographic response was independently verified by a radiologist. Results: Between January 2010 and August 2011, 29 patients were identified with a median age of 57 (range 37-71). 26 (92.8%) had ECOG performance status of 0-1. FOFIRINOX was given to 16 patients with metastatic disease, 12 with locally advanced disease, and one with borderline resectable disease. 17 (61%) received the first cycle with a dose reduction in either irinotecan and/or 5-FU dosage. UGT1A1*28/*28 homozygous genotype was found in 4 patients who all received dose reduced irinotecan. 13 patients (46%) were started on G-CSF prophylactically with the first cycle while 5 additional patients (18%) had G-CSF support added in later cycles. Main adverse events were neutropenia (grade 3-4 in 14.2%), and abdominal pain and diarrhea (grade 3-4 in 7% and 4% respectively). One incidence of neutropenic fever was observed. Four patients were hospitalized for treatment-related toxicity while three had therapy discontinued due to intolerance. At present, 19 patients have imaging available to determine efficacy: 5 (26%) had partial response, 12 (63%) stable disease, and 2 (11%) had progression of disease as their best response. For patients with locally advanced disease, 11 out of 12 had clinical benefit on FOLFIRINOX. Conclusions: In our practice, FOLFIRINOX was well tolerated and was efficacious, consistent with previously published data. It was frequently used in the setting of locally advanced disease and had similar benefit and tolerability in this setting.

Imfirst: A phase IIIb, safety, single arm study of carboplatin (CB) or cisplatin (CP) plus etoposide (ET) with atezolizumab (ATZ) in patients with untreated extensive-stage small cell lung cancer (ES-SCLC) in Spain—Primary safety results of the induction phase.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Maria Rosario García Campelo ◽  
Manuel Domine ◽  
Javier De Castro ◽  
Alberto Moreno ◽  
Santiago Ponce Aix ◽  
...  
Keyword(s):  
Adverse Events ◽  
Safety Profile ◽  
Performance Status ◽  
Maintenance Phase ◽  
Tumor Biomarker ◽  
Induction Phase ◽  
Ecog Performance Status ◽  
Serious Adverse Events ◽  
Biomarker Analysis ◽  
Significant Clinical Improvement

8567 Background: Clinical trial (CT) IMpower133 met both primary endpoints and is the first CT to show significant clinical improvement over standard chemotherapy (C) with a good safety profile in first line (1L) ES-SCLC. The addition of ATZ to CB + ET resulted in an OS landmark of 34% and 22% compared to 21% and 16.8% of patients alive at 18 and 24 months respectively versus C. IMfirst evaluates ATZ + CB or CP + ET in a broader patient population than the pivotal study. ECOG Performance status (PS) 2, asymptomatic untreated brain metastases, underlying stable autoimmune diseases and HIV+ pts are eligible. IMfirst also includes the possibility of 6 C induction cycles according to investigator´s choice and consolidation radiotherapy. Methods: To evaluate the safety and efficacy of ATZ added to CB or CP + ET as 1L treatment in an interventional real world setting of ES-SCLC. Exploratory endpoints include tumor biomarker analysis related to ATZ. Results: As of Oct 2020, 117 pts had been enrolled, 105 treated with ATZ + CB + ET and 12 with ATZ + CP + ET. The median age was 65 years (Y) (range 35-89); 84 males; 14 pts (12%) had CNS metastases and 66 pts were current smokers and 50 former smokers, one had never smoked. The PS was 0 in 28 pts (24%), 1 in 75 (64%) and 2 in 14 (12%). The median of cycles of ATZ received was 4 for all the pts (range 1-12) and 2 for the pts (40) in maintenance phase (range 1-8). Number of pts with adverse events (AEs) was 109, 36 with Serious Adverse Events (SAEs) and 63 with AEs. 8 pts had SAEs related to treatment, 4 had adverse events of special interest and 13 pts discontinued the treatment due to AEs: 6 to ATZ, 12 to CB or CP and 10 to ET, 1 patient discontinued ATZ due to a related AE. Table shows the treatment related AEs (TRAEs). No grade 5 TRAEs were reported. Conclusions: IMfirst induction phase analysis confirms the safety profile of ATZ plus C in a broader population of patients. Efficacy, biomarker and further safety analyses will be presented in the future with longer follow up.[Table: see text]

scholarly journals Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Florence Chamberlain ◽  
Sheima Farag ◽  
Constance Williams-Sharkey ◽  
Cecilia Collingwood ◽  
Lucia Chen ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Individual Risk ◽  
Duration Of Treatment ◽  
Ecog Performance Status ◽  
Third Line ◽  
Grade 3 ◽  
Dose Reductions

Abstract Background Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. Methods Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. Results Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8–14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2–28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3–4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. Conclusion Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

Fludarabine and Mitoxantrone for the Refractory Relapse Treatment of B-Cell Low-Grade Non-Hodgkin Lymphoma (NHL): LACOHG First Interim Report (Latin American Cooperative Oncology Hematology Group).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4665-4665
Author(s):  
Severiano Baltazar-Arellano ◽  
Patricia Pimentel ◽  
Luis Vera ◽  
Fernando Bezares ◽  
Jose Málaga ◽  
...  
Keyword(s):  
B Cell ◽  
Latin American ◽  
Progressive Disease ◽  
Performance Status ◽  
Previous Treatment ◽  
Low Grade ◽  
Ecog Performance Status ◽  
Ann Arbor ◽  
Grade 3

Abstract Background: fludarabine (F) is licensed for the management of indolent non Hodgkin’s lymphoma in countries such as Canada and Switzerland. Clinical evidence suggests that fludarabine monotherapy is as least as effective, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL achieving objective response rates. Better response rates can be achieved combining F with Mitoxantrone (M) in low grade NHL even in refractory relapsed (RR) patients (pts). The Latin American Cooperative Oncology Hematology Group (LACOHG) proposed a multicenter study in Latin American countries in 2002 to use FM in RR B-cell low grade NHL. Aims: to assess the response rate, safety, disease free survival (DFS) and overall survival (OS) of FM in RR B-cell low grade NHL during (2003–2006). Methods: Forty-eight patients in the period of January 2003 to February 2006 were evaluated. Forty-four pts. had follicular lymphoma and 4 small lymphocytic lymphoma. Median age 63.5 years old (range: 24–83). Gender: female 56% and male 44%. Inclusion criteria for low grade NHL-LG was: any previous treatment excluding autologous transplantation, Ann Arbor stage II to IV, age > 18 years old, ECOG performance status 0–2 and written informed consent. ECOG performance status 0: 2%, 1: 71% and 2: 27%. Ann Arbor staging: II: 2%, III: 29% and IV: 69%. International Prognostic Index (IPI): 0–1: 19%, 2–3: 71% and 4–5: 10%. Median previous treatment was 1 (range: 1–3). FM treatment consisted of F 25 mg/m2 i.v. (day 1–3) and M 10 mg/m m2 i.v. (day 1) each 28 days for 6–8 cycles. Results: on this low grade NHL cohort the overall response rate (ORR was 81%; progressive disease and non-response 19%. With a median follow up of 17 months, OS at 24 months was 86% (DE 5.2%) and DFS at 24 months 57.1% (DE 11.3%). LDH in serum was not an adverse prognostic factor for DFS and OS. Safety: on the 286 cycles in 48 pts, the toxicity was: 18 episodes of grade 3-4 neutropenias, 15 episodes of grade 3-4 thrombocytopenia, 7 episodes of grade 1–2 nausea/vomiting, grade 1–2 diarrhea in 4 pts, 8 pts were admitted to the clinic, 11 fever episodes, 2 allopecia, 4 pts developed grade 1–2 peripheral neuropathy and infections 7%: one case herpes zoster. Mortality rate: 12,5% (6/48 patients), 5 of them because progressive disease. No cardiac toxicity was reported. Conclusions: FM is an effective and safe treatment for RR low grade NHL. A longer follow up and a larger trial, might be needed to confirm these results in a multicenter, randomized study. DFS with FM in RR low grade NHL : LACOHG DFS with FM in RR low grade NHL : LACOHG

A randomized, double-blind phase II study of the oral tyrosine kinase inhibitor (TKI) axitinib (AG-013736) in combination with docetaxel (DOC) compared to DOC plus placebo (PL) in metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1003-1003 ◽  
Author(s):  
H. S. Rugo ◽  
A. Stopeck ◽  
A. A. Joy ◽  
S. Chan ◽  
S. Verma ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Hazard Ratio ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Grade 3

1003 Background: Single-agent DOC is commonly used to treat MBC. Axitinib (AG) is a potent TKI of VEGFRs. A phase I lead-in study identified 80 mg/m2 q3wks of DOC in combination with 5 mg BID of AG as the recommended phase 2 dose. The primary objective was to determine whether the time to progression (TTP) of AG+DOC arm is superior to DOC+PL. Methods: Pts with no prior chemotherapy for MBC and =12 mos from adjuvant chemotherapy (aCT), measurable disease, ECOG performance status (PS) of 0–2, and no uncontrolled brain metastases were randomly assigned (2:1) to receive treatment with either DOC+AG or DOC+PL without prophylactic growth factor in cycle 1. Tumor measurements were performed q9wks. Pts were stratified according to estrogen receptor (ER) status, prior aCT and PS (0–1 or 2). Results: A total of 168 pts were randomized. 92 pts had received prior aCT, 27 of whom received a prior taxane. Treatment arms were well balanced for prior adjuvant and taxane therapy. A median of 7 cycles of AG+DOC (range: 1–18) and 7 cycles of DOC+PL (range: 1–23) were administered. The most common non-hematologic adverse events observed in the AG+DOC arm included diarrhea (60%), nausea (53%), alopecia (51%), fatigue (49%), stomatitis (44%) and vomiting (40%). Grade 3/4 adverse events that were increased with AG+DOC vs DOC included febrile neutropenia (16 vs 7%), fatigue (13 vs 5%), stomatitis (13 vs 2%), diarrhea (11 vs 0%) and hypertension (5 vs 2%). Other grade 3/4 hematologic toxicities were similar in both arms. The median TTP (by RECIST) was 8.2 mo with AG+DOC arm and 7 mo with DOC+PL arm with a hazard ratio of 0.73 (prespecified, one-sided p=0.052). The overall response rate (ORR) was 40% for AG+DOC arm and 23% for DOC+PL arm (p=0.038). In a hypothesis-generating subgroup analysis, the median TTP in patients receiving prior aCT was 9.0 mo with AG+DOC arm and 6.3 mo with DOC+PL arm with a hazard ratio of 0.54 (p=0.012). Within this stratum, ORR was 45% for AG+DOC arm and 13% for DOC+PL arm (p=0.003). Conclusions: The anti-angiogenic TKI AG combined with DOC (80 mg/m2 q3wks) as first line therapy for MBC has an acceptable safety profile and promising anti-tumor activity. No significant financial relationships to disclose.

A phase Ib trial of FOLFIRINOX plus saridegib, an oral hedgehog (Hh) inhibitor, in pts with advanced pancreatic cancer (PDAC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3105-3105 ◽  
Author(s):  
Andrew H. Ko ◽  
Noelle K. LoConte ◽  
Emily Kantoff ◽  
Robert W. Ross ◽  
Elizabeth G. Trehu ◽  
...  
Keyword(s):  
Trial Design ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Clinical Trial Design ◽  
Concurrent Administration ◽  
Phase Ib ◽  
Grade 3 ◽  
Ecog Ps ◽  
Dose Levels

3105 Background: FOLFIRINOX has emerged as the optimal 1st-line treatment option for pts with advanced PDAC and good performance status; whether it can serve as the backbone upon which to add targeted agents in clinical trial design remains uncertain. The goal of this multicenter phase Ib study is to evaluate FOLFIRINOX in combination with saridegib, a novel oral agent that inhibits the Hh signaling pathway. In preclinical models of PDAC, saridegib increases chemotherapy delivery by depleting peritumoral stroma and increasing vascularity. Methods: Pts with previously untreated metastatic or locally advanced PDAC and ECOG PS 0-1 were eligible. Treatment consists of once-daily saridegib with concurrent administration of biweekly FOLFIRINOX (omitting the 5-FU bolus). A 3+3 dose escalation design was used (see dose levels below). Prophylactic WBC growth factor support is mandated.  DLT definitions include ALT/AST ≥10x ULN, grade 4 plts or ANC ≥5 d, or grade 3-4 nonheme toxicity. CT scans are obtained every 4 cycles. Limited PK analyses are performed. Results: Seven pts have been enrolled at the first 2 dose levels. Grade 1-2 AEs include GI (N/V/D), dehydration, fatigue, and LFT abnormalities. There was one DLT (grade 3 ALT elevation) at DL2. Other serious toxicities seen include grade 3 nausea (DL1) and grade 3 diarrhea (DL2). Tumor shrinkage has been observed in all 4 pts at DL1, ranging from 17-54%, with 2 unconfirmed PRs. Final MTD determination and updated safety and efficacy data will be presented at the meeting. Conclusions: A modified FOLFIRINOX regimen can be safely administered in combination with novel agents in clinical trials of PDAC. While saridegib was not beneficial when added to gemcitabine in a separate randomized phase II study, early evidence of significant responses on the current trial suggests that a more intensive chemotherapy platform may represent a preferable strategy in PDAC trial design. [Table: see text]

Palliative radiotherapy for prostate cancer: Outcomes of a weekly schedule of 6 fractions of 5 or 6Gy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 160-160 ◽  
Author(s):  
Shaun P. Tolan ◽  
Peter Mbanu ◽  
Richard C. Walshaw ◽  
Peter Robson ◽  
Chinnamani Eswarvee ◽  
...  
Keyword(s):  
Survival Data ◽  
Performance Status ◽  
Locally Advanced ◽  
Intensity Modulated Radiotherapy ◽  
Palliative Radiotherapy ◽  
Weekly Schedule ◽  
Ecog Performance Status ◽  
Fractionation Schedule ◽  
Grade 3 ◽  
Castrate Resistant

160 Background: In the current era of PSA screening and advances in image guided intensity modulated radiotherapy, not all patients with carcinoma of the prostate (CaP) are suitable for radical radiotherapy (RT). Some patients have locally advanced disease and are unfit for radical RT or have significant local symptoms with coexisting metastatic disease. The outcomes of a weekly palliative RT schedule of 6 x 5 or 6Gy fractions are reported. Methods: This retrospective analysis identified 80 patients with CaP who received palliative prostate RT between 2003 and 2007. 62 patients received six, weekly fractions of 3D conformal RT and are included in this study. Clinico-pathological data of the cases are presented along with the clinical outcomes and survival data. Median follow up was 16.5 months. Results: 62 patients (median age 70 yrs), received 30Gy (87%) or 36Gy (10%) in 6 fractions over 6 weeks. Two patients received 27Gy. Gleason score at diagnosis was ≤6, 7, or 8–10 in 21%, 16% and 45% of cases respectively and was associated with a median PSA of 53ng/ml, and T3/4 stage in 59%. The median time from diagnosis to RT was 15.9 months and prior to RT, treatment included hormone therapy (100%), TURP (60%) and chemotherapy (13%). Disease was metastatic in 68% and castrate resistant in 77% of cases. ECOG performance status was 0–1 in 44% and 2–3 in 24%. No patients with PS 4 were treated over 6 weeks. Indications for RT were obstructive urinary symptoms (69%), pain (44%), haematuria (35%), obstructive bowel symptoms (23%), and rectal bleeding (2%). At 3–6 months post-RT the frequency of these symptoms was 27%, 13%, 4%, 17% and 2% respectively. RTOG grade 3 or 4 bladder toxicity was 18% and grade 3 or 4 bowel toxicity was 6%. Median overall survival after RT was 16.0 months and on multivariate analysis lower pre-RT PSA and prior use of chemotherapy were predictive of improved survival. Conclusions: A weekly fractionation schedule of 5 or 6Gy over 6 weeks provides effective palliation, particularly for the symptoms of urinary obstruction, pain and haematuria, and is associated with acceptable toxicity. The prognosis of this group of patients remains poor, but can be improved by the use of chemotherapy if clinically appropriate.

LAPACT: An open-label, multicenter phase II trial of nab-paclitaxel (nab-P) plus gemcitabine (Gem) in patients (pts) with locally advanced pancreatic cancer (LAPC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS477-TPS477 ◽  
Author(s):  
Philip Agop Philip ◽  
Jill Lacy ◽  
Scot D. Dowden ◽  
Javier Sastre ◽  
Venu Gopal Bathini ◽  
...  
Keyword(s):  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Open Label ◽  
Primary Tumors

TPS477 Background: In pts with LAPC, more effective systemic therapies may be associated with improved local control, delay of metastasis, and overall survival (OS). The phase III MPACT trial in pts with metastatic PC demonstrated longer OS (median, 8.7 vs 6.6 mos; HR, 0.72; P < 0.001) and an ≈ 3-fold greater shrinkage of primary tumors with nab-P + Gem vs Gem alone (−22.15% vs −7.02%), raising the possibility of improved local PC control with nab-P + Gem. LAPACT will assess the efficacy and safety of nab-P + Gem in LAPC. Methods: LAPACT will enroll treatment-naive pts (planned n ≈ 110) in the United States, Canada, and Europe with Eastern Cooperative Oncology Group performance status ≤ 1, confirmed unresectable LAPC, no distant metastases, and adequate organ function. Pts with mixed-origin tumors, any other malignancy within 5 years, peripheral neuropathy grade > 1, or clinically significant ascites are ineligible. Pts will receive nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 of each 28-day cycle. Pts without progressive disease (PD) or unacceptable toxicity after 6 cycles will receive investigator’s choice of surgery, chemoradiotherapy, or continued nab-P + Gem. If a major response is observed, surgery may occur prior to completing 6 cycles of nab-P + Gem. The primary endpoint is time to treatment failure (TTF; time from first therapy dose to discontinuation due to PD, start of a new non–protocol-defined anti-cancer therapy, or death). The study design allows for 80% power at a 1-sided α of 0.05 to detect a 30% increase over the 5.1-month median TTF observed for nab-P + Gem in the MPACT study. The secondary endpoints are disease control rate (DCR) after 6 cycles, overall response rate, progression-free survival, OS, safety, and quality of life. The exploratory endpoint is correlation of changes in circulating nucleic acids with PD and treatment response. An interim DCR analysis will occur after all pts have completed 6 cycles of nab-P + Gem, discontinued therapy due to PD, died, or started a new non–protocol-defined therapy before completing 6 cycles of therapy. Enrollment is ongoing (first pt enrolled in April 2015). Clinical trial information: NCT02301143.

Comparative effectiveness of proton therapy versus photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6521-6521 ◽  
Author(s):  
Brian Christopher Baumann ◽  
Nandita Mitra ◽  
Joanna Harton ◽  
Ying Xiao ◽  
Andrzej Wojcieszynski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Adverse Events ◽  
Comparative Effectiveness ◽  
Performance Status ◽  
Locally Advanced ◽  
Grade 3 ◽  
Unplanned Hospitalizations ◽  
Locally Advanced Cancer ◽  
Disease Free

6521 Background: Concurrent chemo-radiotherapy is standard-of-care curative treatment for many cancers, but is associated with substantial morbidity. Proton therapy may increase the tolerability or effectiveness of concurrent chemo-radiotherapy by reducing radiation to normal tissues. Methods: We conducted a comparative effectiveness study of adult non-metastatic cancer patients treated with curative intent with proton chemo-radiotherapy vs. photon chemo-radiotherapy from 2011-2016 at the University of Pennsylvania. Re-irradiation and disease sites treated with photon-only therapy were excluded. Data on adverse events and survival was gathered prospectively. Primary endpoint was 90-day adverse events associated with unplanned hospitalizations (CTCAEv4 grade ≥3 adverse events). Secondary endpoints included decline in ECOG performance status during treatment, 90-day grade ≥2 adverse events, disease-free survival (DFS) and overall survival (OS). Modified Poisson regression models with inverse propensity score weighting were fit for both outcomes. Propensity scores were estimated using an ensemble machine-learning approach. Results: 1,483 patients were included (391 proton/1,092 photon). Proton patients were significantly older (median 66 vs. 61), had less favorable Charlson-Deyo comorbidity scores (median 3.0 vs. 2.0), and had lower integral radiation dose to tissues outside the target (p < 0.05 for all). Baseline toxicity and performance status were similar (p > 0.05). In propensity score weighted-analyses, proton chemo-radiotherapy was associated with significantly lower relative risk (RR) of 90-day grade ≥3 adverse events [11.5%(95%CI 8.3-14.7%) for protons; 27.6%(95%CI 24.9-30.2%) for photons; RR 0.31, 95%CI 0.15-0.66, p < 0.01]; 90-day grade ≥2 adverse events (RR 0.78, 95%CI 0.65-0.93, p < 0.01); and decline in performance status during treatment (RR 0.51, 95%CI 0.37-0.71, p < 0.01). There was no difference in DFS or OS. Conclusions: In adults with locally advanced cancer, proton chemo-radiotherapy was associated with significantly reduced acute adverse events causing unplanned hospitalizations with similar disease-free and overall survival.

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