Patterns of failure in a phase II trial of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) for resectable and borderline resectable (BLR) pancreatic cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 482-482 ◽  
Author(s):  
Jordan Kharofa ◽  
Michelle Lynn Mierzwa ◽  
Olugbenga Olanrele Olowokure ◽  
Jeffrey J. Sussman ◽  
Tahir Latif ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cumulative Incidence ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Local Failure ◽  
Borderline Resectable ◽  
Target Volumes ◽  
Secondary Endpoints ◽  
Optimal Target ◽  
Grade 3

482 Background: There is emerging interest in the role of SBRT in locally advanced pancreas cancer, however little prospective data exists examining the safety, efficacy, and optimal target volumes for SBRT in the neoadjuvant setting for resectable or BLR pancreatic cancer. Methods: Eighteen patients were enrolled from 11/2014-6/2017. SBRT was delivered to the tumor and abutting vessel with fiducials/compression and a 3 mm PTV margin to 33 Gy (6.6 Gyx5fxn) with an optional elective PTV to 25 Gy (5 Gyx5fxn) customized to the nodal space and mesenteric vessels. Patients without progression underwent surgery 4-6 weeks following SBRT. The primary endpoint is ≥ Grade 3 acute and late GI toxicity. Secondary endpoints included overall survival (OS), progression-free survival (PFS),and cumulative incidence of local failure (LF). LF is defined as recurrence within conventional RT volumes from the time of resection to local failure or last CT with no progression. Local failures were fused to planning CTs for dose quantification. Results: Thirteen patients had BLR tumors due to arterial abutment (n = 7) or SMV encasement (n = 8); 3 patients had resectable tumors. All patients received 4 months of gemcitabine/nab-paclitaxel (n = 13) or FOLFIRNOX (n = 5) prior to SBRT. There were no ≥ Grade 3 acute or late GI events. Metastases were noted in 6 patients (33%) at restaging or surgery. Surgery was performed in 12 patients (67%) with 11 (92%) R0 resections. Median OS and PFS are 21 months and 11 months, respectively. Progression occurred in 67% (8/12) of resected patients with first site of failure as distant (n = 3, 38%), local only (n = 4, 50%), and local and distant (n = 1,13%). The cumulative incidence of LF at 12 months from resection was 50%. All LF were outside to the PTV33 with median D90 of 11.5 Gy (4-25 Gy), V25 Gy of 51% (0-90%), and V33 Gy of 45% (0-52%). Conclusions: SBRT as a component of neoadjuvant therapy was well tolerated. However, local failures were predominantly observed outside the PTV33 volume within conventional RT volumes. Therefore, the durability of local control after SBRT in the neoadjuvant setting relative to chemoradiation merits close examination. Clinical trial information: NCT02208024.

Modified gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer (MPC): A single-institution experience.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 366-366 ◽  
Author(s):  
Kavya Krishna ◽  
Marlo A. Blazer ◽  
Lai Wei ◽  
Daniel H. Ahn ◽  
Christina Sing-Ying Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Cost Savings ◽  
Progression Free Survival ◽  
Borderline Resectable ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Cost Of Drugs

366 Background: The combination of gemcitabine and nab-paclitaxel (GA) in first line treatment (tx) of MPC has a modest survival advantage over gemcitabine (gem) alone, but adds significant toxicities (tox) and increased cost. Based on data suggesting that biweekly administration (adm) of gem-based combinations preserves efficacy and improves tox profile, our institution adopted a modified regimen of GA (mGA). Methods: This is a retrospective analysis of a prospectively maintained database of patients (pts) with pancreatic cancer treated with gem (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1 and 15 of a 28-day cycle. Survival curves were estimated using Kaplan-Meier method, with alive pts censored at time of last follow-up. Cost of tx includes cost of drugs, adm, and tox. Results: Of total 69 pts treated with mGA for MPC, locally advanced, or borderline resectable disease, 63 pts were evaluable for tox (table 1). A total of 49 pts (47 evaluable for response) received mGA for previously untreated MPC, with median progression free survival of 4.8 months(mo) (95% CI 2.6,7.4) and overall survival of 11.1 mo (95% CI 5.3,not reached). Overall, 27% of pts experienced neurotoxicity with rate of grade 3 tox of < 2%, and 8% required growth factors (GF). Average cost savings was $5500/pt/month with mGA compared to standard GA, excluding GF cost which was lower with mGA. Conclusions: A less intense regimen of GA maintains efficacy while significantly improving tox profile and cost in pts with MPC. [Table: see text]

A randomized phase II clinical trial of gemcitabine, oxaliplatin, erlotinib combination chemotherapy versus gemcitabine and erlotinib in previously untreated patients with locally advanced or metastatic pancreatic cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 344-344 ◽  
Author(s):  
Sung Hee Lim ◽  
Jina Yun ◽  
Min-Young Lee ◽  
Han Jo Kim ◽  
Kyoung Ha Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Response Rate ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Overall Response ◽  
Significant Difference ◽  
Common Grade ◽  
Secondary Endpoints ◽  
Grade 3

344 Background: Erlotinib is the only targeted agent in combination with gemcitabine showing significantly improved outcomes in pancreatic cancer. Although combining platinum agent with gemcitabine has not provided clear survival benefit over gemcitabine alone, gemcitabine plus platinum resulted in improved response rate and progression-free survival (PFS). We tried to evaluate whether the addition of oxaliplatin to gemcitabine/erlotinib confers a clinical benefit to patients with locally advanced or metastatic pancreatic cancer. Methods: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T (gemcitabine 1000mg/m2 IV and oxaliplatin 50mg/m2 IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks) or GT (gemcitabine 1000mg/m2 IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks). The primary endpoint was overall response and secondary endpoints included PFS, overall survival (OS) and toxicity. Results: Between May 2013 and April 2016, 65 patients were randomly assigned to treatment group (33 in GEMOX-T arm, 32 in GT arm). The median age of all patients was 61 years (range, 41-76) and about 80% of patients had metastatic disease. The overall response rate was 18.2 % in GEMOX-T arm and 6.2% in GT arm ( P = 0.051). The disease control rate was significantly superior in GEMOX-T arm compared to GT arm (72.7% vs. 43.8%, P = 0.019), with 1 patient in GEMOX-T group continuing the treatment with stable disease. After a median follow up of 19.7 months, there was significant difference in PFS: the median PFS were 3.9 months for GEMOX-T arm and 1.4 months for GT arm (Hazard ratio: 0.58, 95% CI 0.35-0.96, P = 0.037). However, it did not translate to improvement of OS (median OS; 6.2 m for GEMOX-T arm, 5.1 m for GT arm, P = 0.118). The most common grade ≥ 3 hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). Conclusions: The addition of oxaliplatin to 1st line gemcitabine/erlotinib regimen demonstrated higher response rate and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

scholarly journals P-P15 Margin Accentuation Irreversible Electroporation in Stage III Pancreatic Cancer: A Systematic Review

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Dhya Al-Leswas ◽  
Bathiya Ratnayake ◽  
Ghazaleh Mohammadi-Zaniani ◽  
Peter Peter Littler ◽  
Gourab Sen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Progression Free Survival ◽  
Stage Iii ◽  
R0 Resection ◽  
Weighted Mean ◽  
Borderline Resectable ◽  
Grade 3

Abstract Background The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). Methods A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies.  Results Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58–64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3–5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7–15). The weighted-mean overall survival was 22 months (95% CI 20–23 months) and 8 months (95% CI 1–32 months) for MA IRE and IRE alone, respectively. Conclusions Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.

scholarly journals Margin Accentuation Irreversible Electroporation in Stage III Pancreatic Cancer: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3212
Author(s):  
Bathiya Ratnayake ◽  
Dhya Al-Leswas ◽  
Ghazaleh Mohammadi-Zaniani ◽  
Peter Littler ◽  
Gourab Sen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Progression Free Survival ◽  
Stage Iii ◽  
R0 Resection ◽  
Weighted Mean ◽  
Borderline Resectable ◽  
Grade 3

The present systematic review aimed to summarise the available evidence on indications and oncological outcomes after MA IRE for stage III pancreatic cancer (PC). A literature search was performed in the Pubmed, MEDLINE, EMBASE, SCOPUS databases using the PRISMA framework to identify all MA IRE studies. Nine studies with 235 locally advanced (LA) (82%, 192/235) or Borderline resectable (BR) PC (18%, 43/235) patients undergoing MA IRE pancreatic resection were included. Patients were mostly male (56%) with a weighted-mean age of 61 years (95% CI: 58–64). Pancreatoduodenectomy was performed in 51% (120/235) and distal pancreatectomy in 49% (115/235). R0 resection rate was 73% (77/105). Clavien Dindo grade 3–5 postoperative complications occurred in 19% (36/187). Follow-up intervals ranged from 3 to 29 months. Local and systematic recurrences were noted in 8 and 43 patients, respectively. The weighted-mean progression free survival was 11 months (95% CI: 7–15). The weighted-mean overall survival was 22 months (95% CI 20–23 months) and 8 months (95% CI 1–32 months) for MA IRE and IRE alone, respectively. Early non-randomised data suggest MA IRE during pancreatic surgery for stage III pancreatic cancer may result in increased R0 resection rates and improved OS with acceptable postoperative morbidity. Further, larger studies are warranted to corroborate this evidence.

Phase I Trial of the Human Immunodeficiency Virus Protease Inhibitor Nelfinavir and Chemoradiation for Locally Advanced Pancreatic Cancer

2008 ◽  
Vol 26 (16) ◽  
pp. 2699-2706 ◽  
Author(s):  
Thomas B. Brunner ◽  
Matthias Geiger ◽  
Gerhard G. Grabenbauer ◽  
Marga Lang-Welzenbach ◽  
Tine S. Mantoni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Peritoneal Metastasis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Hiv Protease ◽  
Hiv Protease Inhibitors ◽  
Borderline Resectable ◽  
Stent Occlusion ◽  
Positron Emission ◽  
Grade 3

PurposePreclinically, HIV protease inhibitors radiosensitize tumors with activated PI3-kinase/Akt pathway. We determined the toxicity of nelfinavir chemoradiotherapy in borderline resectable and unresectable pancreatic cancer.Patients and MethodsOral nelfinavir (2 × 1,250 mg) was started 3 days before and continued throughout chemoradiotherapy to 50.4 Gy (boost, 59.4 Gy) in 12 patients. Two gemcitabine dose levels (DL) were tested (200 mg/m2and 300 mg/m2on days 1, 8, 22, and 29). Cisplatin was administered on the same days at 30 mg/m2. Phospho-Akt downregulation by nelfinavir was monitored by immunoblotting in patient leukocytes. Restaging positron emission tomography (PET)/computed tomography (CT) and CA19-9 levels served to assess response, and responding tumors were resected.ResultsAt each DL, five of six patients completed chemoradiotherapy, and two of 12 patients had incomplete chemoradiotherapy because of clinical depression (DL1) and peritoneal metastasis (DL2). Grade 4 toxicities were a transaminase elevation (DL2) as a result of biliary stent occlusion and acute cholecystitis as a result of peritoneal metastasis (DL2). Stent occlusions led to dose-limiting toxicities of grade 3 liver enzyme and bilirubin elevations (two patients at DL1, one patient at DL2). Grade 3 nausea and vomiting occurred in a DL2 patient, and weight loss occurred in a DL1 patient who refused supportive feeding. Secondary complete resection was possible in six of 10 patients with complete chemoradiotherapy, including one tumor with pathologic sterilization. Partial CT responses were observed in five of 10 patients who completed chemoradiotherapy. Of nine patients assessable by PET,responses were complete in five patients and partial patients, and stable disease was observed in two patients.ConclusionThe combination of nelfinavir and chemoradiotherapy showed acceptable toxicity and promising activity in patients with pancreatic cancer.

scholarly journals Neoadjuvant treatment for locally advanced unresectable and borderline resectable pancreatic cancer: oncological outcomes at a single academic centre

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e000929
Author(s):  
Susana Roselló ◽  
Claudio Pizzo ◽  
Marisol Huerta ◽  
Elena Muñoz ◽  
Roberto Aliaga ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Progression Free Survival ◽  
Rank Test ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Curative Intent ◽  
Kaplan Meier ◽  
Dismal Prognosis

IntroductionPancreatic cancer (PC), even in the absence of metastatic disease, has a dismal prognosis. One-third of them are borderline resectable (BRPC) or locally advanced unresectable PC (LAUPC) at diagnosis. There are limited prospective data supporting the best approach on these tumours. Neoadjuvant chemotherapy (ChT) is being increasingly used in this setting.MethodsThis is a retrospective series of consecutive patients staged as BRPC or LAUPC after discussion in the multidisciplinary board (MDB) at an academic centre. All received neoadjuvant ChT, followed by chemoradiation (ChRT) in some cases, and those achieving enough downstaging had a curative-intent surgery. Descriptive data about patient’s characteristics, neoadjuvant treatments, toxicities, curative resections, postoperative complications, pathology reports and adjuvant treatment were collected. Overall survival (OS) and progression-free survival was calculated with Kaplan-Meier method and log-rank test.ResultsBetween August 2011 and July 2019, 49 patients fulfilled the inclusion criteria, and all of them received neoadjuvant ChT. Fluorouracil+folinic acid, irinotecan and oxaliplatin was the most frequently used scheme (77%). The most prevalent grade 3 or 4 toxicities were neutropenia (26.5%), neurotoxicity (12.2%), diarrhoea (8.2%) and nausea (8.2%). 18 patients (36.7%) received ChRT thereafter. In total, 22 patients (44,9%) became potentially resectable and 19 of them had an R0 or R1 pancreatic resection. One was found to be unresectable at surgery and two refused surgery. A vascular resection was required in 7 (35%). No postoperative deaths were observed. Postoperative ChT was given to 12 (66.7%) of resected patients. Median OS of the whole cohort was 24,9 months (95% CI 14.1 to 35.7), with 30.6 months for resected and 13.1 months for non-resected patients, respectively (p<0.001).ConclusionA neoadjuvant approach in BRPC and LAUPC was well tolerated and allowed a curative resection in 38.8% of them with a potential improvement on OS.

Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14614-e14614 ◽  
Author(s):  
Hemchandra Mahaseth ◽  
John S. Kauh ◽  
Edith Brutcher ◽  
Natalyn Nicole Hawk ◽  
Sungjin Kim ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Emory University ◽  
Grade 3

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m2 CIVI over 46 hours, leucovorin 400 mg/m2, oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.

Impact of renal function on the efficacy and safety of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 301-301
Author(s):  
Satoshi Kobayashi ◽  
Makoto Ueno ◽  
Gakuto Ogawa ◽  
Akira Fukutomi ◽  
Masafumi Ikeda ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Renal Function ◽  
Renal Dysfunction ◽  
Adverse Reactions ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Efficacy And Safety ◽  
Concurrent Radiotherapy ◽  
Secondary Endpoints ◽  
Grade 3

301 Background: S-1 is an oral agent consisting of a mixture of tegafur which is a prodrug of 5-fluorouracil (5-FU), 5-chloro-2,4-dihydroxypyrimidine (DHP) and potassium oxonate. Serum concentration of 5-FU increases in case of renal dysfunction due to decrease of DHP excretion into urine. The aim of this study was to evaluate the influence of renal function to the efficacy and safety of S-1 with concurrent radiotherapy (RT) for locally advanced pancreatic cancer (LAPC). Methods: This study was an integrated exploratory analysis of JCOG1106 and LAPC- S1RT, in which pts with LAPC received RT (50.4Gy/28 fr over 5.5 weeks) and concurrent S-1 (40 mg/m2/dose, bid. on the day of irradiation). Eligibility criteria for this study were pts who received both irradiation and S-1 at least once without induction chemotherapy, and who had creatinine clearance (CCr) ≥ 50 ml/min at the time of registration. We assigned pts into high (≥ 80 ml/min) and low (< 80 ml/min) CCr groups. The primary endpoint was the incidence of ≥ Grade 3 adverse reactions (ARs). Secondary endpoints were the incidence of ≥ Grade 2 gastrointestinal ARs (GI-ARs) defined as anorexia, nausea, vomiting, diarrhea and mucositis oral, relative dose intensity of S-1, CA19-9 response, progression-free survival, and overall survival. Results: Fifty and 59 pts were included in this study from JCOG1106 and LAPC-S1RT, respectively. Median age was 65 years old (range: 31–80), and 57 pts were male. Median CCr was 80.4 ml/min. High CCr group included 57 pts and the median was 97.5 ml/min (range 80.0–194.6), and low CCr group included 52 pts and the median was 64.4 ml/min (range 50.0–78.3). Low CCr group tended to have more ≥ Grade 3 ARs and ≥ Grade 2 GI-ARs compared to high CCr group (30.8% vs. 15.8% and 51.9% vs. 36.8%). However, no evident tendencies were observed in other secondary endpoints. Multivariable analysis showed risk ratio of low CCr group for ≥ G3 ARs was 1.493 [95% CI: 0.710–3.145], although risk ratio of females was 2.486 [95% CI: 1.043–5.924]. Conclusions: Our study indicated that renal dysfunction may increase adverse reactions in the treatment of S-1 with concurrent RT for LAPC, and we should pay attention to renal function and consider for dose reduction.

Phase II Study of Induction Chemotherapy with Gemcitabine plus 5-Fluorouracil Followed by Gemcitabine-Based Concurrent Chemoradiotherapy for Unresectable Locally Advanced Pancreatic Cancer

2006 ◽  
Vol 92 (6) ◽  
pp. 481-486 ◽  
Author(s):  
Ender Kurt ◽  
Meral Kurt ◽  
Ozkan Kanat ◽  
Sibel Kahraman Cetintas ◽  
Sevilcan Aygun ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Disease Stabilization ◽  
Grade 3

Aims and background To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). Patients and methods Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. Results After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). Conclusions The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incor-poration of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

Randomized phase III study of adjuvant versus progression-triggered treatment with gemcitabine (G) after radical cystectomy (RC) for locally advanced bladder cancer (LABC) in patients not suitable for cisplatin-based chemotherapy (CBC) (AUO-trial AB22/00).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 250-250 ◽  
Author(s):  
Jan Lehmann ◽  
Michael Kuehn ◽  
Claus Fischer ◽  
Bjoern Volkmer ◽  
Friedrich von Rundstedt ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Intention To Treat ◽  
Kaplan Meier ◽  
Node Positive Disease ◽  
Secondary Endpoints ◽  
The Difference ◽  
Grade 3

250 Background: Cisplatin-based chemotherapy (CBC) has been widely used in trials of adjuvant therapy for LABC after RC. A high proportion of patients are unfit for CBC after RC for LABC. We therefore performed a prospective randomized phase III trial on G-monotherapy administered as adjuvant therapy (G-adj) vs in case of progression (G-prog) in pts not suitable for CBC. Methods: Between 7/2000 and 12/2008 120 of 178 planned pts with LABC unfit for CBC were randomized between 6 adjuvant cycles of G (q3w) starting within 12 wks after RC and G in case of disease progression. The primary endpoint of the trial was progression-free survival (PFS). Secondary endpoints included cancer-specific (CSS) and overall survival (OS) as well as treatment related toxicity. Results: The trial of 178 planned pts was closed early due to slow accrual. Of 120 randomized pts from 29 centers 114 were eligible for analysis. Median age of 81 male and 33 female pts was 72 (45-82) years. Lymph-node positive disease was found in 52/114 (47%) of pts at the time of surgery. The intention-to-treat analysis demonstrated a 10% difference in PFS after 3 years 50% (G-adj) vs 40% (G-prog) with a median PFS of 23 mo (G-adj) vs 17 mo (G-prog). The difference in PFS was not statistically significant (nss) (p= 0.335; HR 1.375, 95%CI 0.719 - 2.627). CSS at 3ys: 56% (G-adj) vs 50% (G-prog) with a median CSS of 49 mo (G-adj) vs 38 mo (G-prog). The difference in CSS was nss (p= 0.622; HR 1.166, 95%CI 0.632 - 2.149). OS at 3ys: 49% (G-adj) vs 48% (G-prog) with a median OS of 32 mo (G-adj) vs 31 mo (G-prog). The difference in OS was nss (p= 0.426; HR 1.225, 95%CI 0.743 - 2.018). Treatment with G was usually well tolerated, with less than 15% grade 3/4 toxicities..There was one treatment related death in the G-adj arm. Conclusions: The study-hypothesis of a 15% difference in PFS after 3 years in favor of G-adj vs G-prog could not be confirmed. Nevertheless a marked difference in survival in favor of G-adj was shown by Kaplan-Meier plots regarding PFS, CSS and OS within the first 24 months after RC. Clinical trial information: NCT00146276.

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