Combined chemotherapy and EUS-guided intra-tumoral 32-P implantation for locally advanced pancreatic ductal adenocarcinoma: a pilot study

Endoscopy ◽  
2021 ◽  
Author(s):  
Jeevinesh Naidu ◽  
Dylan Bartholomeusz ◽  
Joshua Zobel ◽  
Romina Safaeian ◽  
William Hsieh ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Adelaide Hospital ◽  
Response To Treatment ◽  
Ductal Adenocarcinoma ◽  
Resection Margins ◽  
R0 Resection ◽  
Royal Adelaide Hospital ◽  
Combined Chemotherapy ◽  
Radioactive Phosphorus ◽  
18Fdg Pet

Aim: This study evaluated clinical outcomes of combined chemotherapy and Endoscopic Ultrasound (EUS) guided intra-tumoral radioactive phosphorus-32 (32P OncoSil) implantation in locally advanced pancreatic adenocarcinoma (LAPC). Methods: Consecutive patients with a new histological diagnosis of LAPC were recruited over 20 months. Baseline CT and 18FDG PET-CT were performed and repeated after 12 weeks to assess response to treatment. Following 2 cycles of conventional chemotherapy, patients underwent EUS-guided 32P OncoSil implantation followed by a further six cycles of chemotherapy. Results: Twelve patients with LAPC (8M:4F; median age 69 years, IQR 61.5-73.3) completed the treatment. Technical success was 100% and no procedural complications were reported. At 12 weeks, there was a median reduction of 8.2cm3 (95% CI 4.95-10.85; p=0.003) in tumour volume, with minimal or no 18FDG uptake in 9 (75%) patients. Tumour downstaging was achieved in 6 (50%) patients, leading to successful resection in 5 (42%) patients, of which 4 patients (80%) had clear (R0) resection margins. Conclusions: EUS guided 32P OncoSil implantation is feasible and well tolerated and was associated with a 42% rate of surgical resection in our cohort. However, further evaluation in a larger randomized multicenter trial is warranted. (32P funded by OncoSil Medical Ltd, equipment and staff funded by the Royal Adelaide Hospital, ClinicalTrials.gov number, NCT03003078).

Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

2021 ◽  
pp. 000313482110111
Author(s):  
Weizheng Ren ◽  
Dimitrios Xourafas ◽  
Stanley W. Ashley ◽  
Thomas E. Clancy
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Resection Margins ◽  
Borderline Resectable ◽  
Stepwise Selection ◽  
R1 Resection ◽  
Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

705 SIGNIFICANCE OF CLEAR CIRCUMFERENTIAL RESECTION MARGIN IN ESOPHAGEAL CANCER

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Catherine Cheang ◽  
Pradeep Patil
Keyword(s):  
Esophageal Cancer ◽  
Multimodal Therapy ◽  
Resection Margin ◽  
Locally Advanced ◽  
Radical Resection ◽  
Resection Margins ◽  
R0 Resection ◽  
Term Survival ◽  
R1 Resection

Abstract   Circumferential resection margins (CRM) of an esophagectomy specimen for oesophageal cancer is a key prognostic factor of overall survival (OS). This retrospective study aims to compare OS of post-esophagectomy patients with CRM of &gt;1 mm (R0) and &lt; 1 mm (R1) with further subgroup analysis of locally advanced T3R0 vs T3R1 resection. Methods A total of 110 esophagectomies conducted between 2010 and 2020 were analysed. We recorded R stage based on pathological CRM &gt;1 mm (R0) or &lt; 1 mm (R1). OS was calculated from the day of surgery to day of death or otherwise censored. All patients underwent multimodal therapy including chemotherapy and similar pre-surgical and post-surgical management. 58 of these patients with pT3 stage esophageal cancer (EC) were selected and compared. Statistical analysis was carried out using SPSS. Results Of 110 patients, 78 (71.5%) patients had a R0 resection. Mean OS in R0 resections was 73 months (6 years) compared to 25.2 months (2 years) in R1 resection (p = 0.001). 58 of the 110 patients were pathological stage T3(pT3) despite downstaging with chemotherapy showing the burden of advanced disease. In patients with stage pT3 (n = 58), 32 patients were R0 resections, and 26 patients had R1 resections. Mean OS in T3R0 resections was 51.5 months compared to 28.5 months in T3R1 resection. OS comparison is significant (p = 0.011). Conclusion This study emphasizes the importance of clear CRM in all patients and especially in locally advanced pT3/T4a esophageal cancer in achieving long term survival. Techniques used to ensure a clear CRM such multimodality therapy combined with surgical radical resection concepts such as mesoesophagectomy should be employed.

Long-term consequences of exenterative surgery for people with pelvic cancer.

2018 ◽  
Vol 36 (7_suppl) ◽  
pp. 118-118 ◽  
Author(s):  
Jane Young ◽  
Michael Solomon ◽  
Daniel Steffens ◽  
Cherry Koh
Keyword(s):  
Quality Of Life ◽  
Locally Advanced ◽  
Resection Margins ◽  
R0 Resection ◽  
Personal Goals ◽  
Pelvic Cancer ◽  
Patient Reported ◽  
Ongoing Pain

118 Background: For people with recurrent or locally advanced pelvic cancer with no evidence of metastatic spread, pelvic exenteration (PE) surgery that achieves clear (R0) resection margins is the only potentially curative treatment option. This extensive, radical surgery can involve removal of the pelvic organs, muscles, nerves and bone, resulting in significant impairment for patients. The aim of this study is to describe the long-term quality of life outcomes for this procedure, specifically to investigate levels of pain, vitality, depression and ability to achieve personal goals among survivors three or more years after surgery. Methods: The Royal Prince Alfred Hospital in Sydney is a national referral center for PE in Australia. Patient-reported outcome measures, including generic (SF36) and colorectal cancer-specific (FACT-C) measures of quality of life (QoL), pain, vitality, depression and self-reported ability to achieve personal goals are assessed pre-surgery, every six months to three years and then annually. Consecutive patients who were three or more years after PE comprised the sample for this study. Trajectories for patient reported outcomes were plotted and the proportion of survivors who experienced ongoing pain, vitality and depression at each time point were calculated. Results: Among 241 patients who were 3 years post-PE, 63 (26%, 95% CI: 21-32%) had died and 3-year QoL assessments were completed by 65 (51%) of survivors. Three years after surgery, mean QoL scores were similar to baseline and remained fairly stable among survivors to 5 years. There was a small decrease over time in the proportion of survivors reporting ongoing pain. From 3 years onwards, approximately 70% (95% CI: 58-79%) of survivors reported ongoing pain and 44% (95% CI: 34-57%) reported some level of depression. However, SF-36 vitality scores increased slightly from a mean of 46.2 pre-PE to 54.0 at 3 years. Conclusions: Despite the extensive nature of PE surgery, the majority of survivors achieved reasonable long-term quality of life. However, high levels of chronic pain and depression indicate ongoing needs for supportive care in this patient group.

Effect of Margin Status on Survival After Resection of Hilar Cholangiocarcinoma in the Modern Era of Adjuvant Therapies

2020 ◽  
pp. 000313482097340
Author(s):  
Michael D. Watson ◽  
Maria R. Baimas-George ◽  
Michael J. Passeri ◽  
Jesse K. Sulzer ◽  
Erin H. Baker ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hilar Cholangiocarcinoma ◽  
Demographic Data ◽  
Locally Advanced ◽  
Resection Margins ◽  
R0 Resection ◽  
Complication Rates ◽  
Curative Intent ◽  
Adjuvant Therapies

Introduction Studies have shown that for patients with hilar cholangiocarcinoma (HC), survival is associated with negative resection margins (R0). This requires increasingly proximal resection, putting patients at higher risk for complications, which may delay chemotherapy. For patients with microscopically positive resection margins (R1), the use of modern adjuvant therapies may offset the effect of R1 resection. Methods Patients at our institution with HC undergoing curative-intent resection between January 2008 and July 2019 were identified by retrospective record review. Demographic data, operative details, tumor characteristics, postoperative outcomes, recurrence, survival, and follow-up were recorded. Patients with R0 margin were compared to those with R1 margin. Patients with R2 resection were excluded. Results Seventy-five patients underwent attempted resection with 34 (45.3%) cases aborted due to metastatic disease or locally advanced disease. Forty-one (54.7%) patients underwent curative-intent resection with R1 rate of 43.9%. Both groups had similar rates of adjuvant therapy (56.5% vs. 61.1%, P = .7672). Complication rates and 30 mortality were similar between groups (all P > .05). Both groups had similar median recurrence-free survival (R0 29.2 months vs. R1 27.8 months, P = .540) and median overall survival (R0 31.2 months vs. R1 38.8 months, P = .736) with similar median follow-up time (R0 29.9 months vs. R1 28.5 months, P = .8864). Conclusions At our institution, patients undergoing hepatic resection for HC with R1 margins have similar recurrence-free and overall survival to those with R0 margins. Complications and short-term mortality were similar. This may indicate that with use of modern adjuvant therapies obtaining an R0 resection is not an absolute mandate.

Retrospective determination of the correlation between the distance of tumor manifestation to peripancreatic arteries and overall survival in primary resected pancreatic ductal adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15745-e15745
Author(s):  
Uwe A Wittel ◽  
Michael Uhl ◽  
Frank Makowiec ◽  
Ulrich Theodor Hopt ◽  
Stefan Fichtner-Feigl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Median Survival ◽  
Average Distance ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Resection Margins ◽  
R0 Resection ◽  
Borderline Resectable ◽  
R1 Resection

e15745 Background: Current guidelines determine the resectability of PDAC by evaluating the contact of the tumor to peripancreatic vasculature. We wanted to evaluate the influence of this distance of the tumor to peripancreatic arteries on the overall survival of patients with primary resection of pancreatic ductal adenocarcinoma. Methods: Preoperative radiographs of 208 consecutive patients after distal pancreatectomy and/or pancreatoduodenectomy operated between 2007 and 2014 were included in the analysis. In reconstructions of CT and MRI data 90° planes to the centerline of the celiac trunc (CT), hepatic artery(HA) and superior mesenteric artery(SMA) were computed with Aquarius Intuition Viewer (V4.4.11, Terarecon). The closest distance between the tumor and the CT /HA and SMA was determined by an experienced pancreatic surgeon and radiologist independently and upon a deviation greater than 3 mm consent was reached by additional review in 33,2% (69/208) of the cases. Results: 176 CT and 32 MRI scans of 208 patients were evaluated. 2.4 % (5/208) of the radiographs were excluded due to insufficient quality. Average distance of the tumor to the CT/HA and SMA was 16.3 and 6.5 mm for PD and 12.7 and 11.0 mm for DP. Distance between the artery and the tumor did not influence the R0 resection rates (overall R0 > 1mm resection margin 64%) and median overall survival was 24.0 months after R0 resection and 13.5 months after R1 resection (log-rank test P < 0.05). Borderline resectable patients (n = 57) showed a median survival of 13.4 months, patients with their tumor 1-5mm distant to the closest artery (n = 65) and greater than 5 mm distance (n = 81) showed a median survival of 20.3 and 32.9 months respectively. Patients with 0-5 and greater than 5 mm distance between arteries and tumor showed a survival benefit from R0 resection (R0/R1 0-5mm 20.3/13.5 months; > 5mm 37.3/12.8 months) while R0 resected borderline resectable patients showed a similar survival than R1 resected patients (R0 12.7months, R1 15.1 months). Conclusions: The negative resection margins in borderline resectable patients not increase the survival when compared to R1 resected patients. Patients with primary R0 resection and initially large distance of the tumor to peripancreatic vasculature show a prolonged survival.

Real-world survival outcomes of using neoadjuvant chemotherapy in pancreatic cancer patients: Findings from the PURPLE clinical registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16755-e16755
Author(s):  
Belinda Lee ◽  
Vincent Witmond ◽  
Amanda Pereira-Salgado ◽  
Koen Degeling ◽  
Julia Shapiro ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Real World ◽  
Locally Advanced ◽  
Asia Pacific ◽  
Resection Margins ◽  
Survival Outcomes ◽  
R0 Resection ◽  
The Impact

e16755 Background: Only a minority of pancreatic cancer patients (pts) are surgical candidates at presentation. Neoadjuvant chemotherapy (NAT) is proposed to increase the proportion of surgical candidates. This study investigates the impact of NAT in routine care of pancreatic cancer. Three cohorts were analysed, patients with early-stage resectable (ER), borderline resectable (BR) and locally advanced (LA) pancreatic cancer. Within these groups, survival outcomes of those undergoing immediate resection (IR) was compared to those receiving NAT with nab-paclitaxel and Gemcitabine (nabPGem) and NAT with FOLFIRINOX. Methods: The PURPLE registry consists of 1492 pancreatic cancer pts from 27 hospitals in Australia, New-Zealand and Singapore, collated between 2016-2019. After exclusion of LA unresectable and metastatic pts (n = 809), 683 pts were included. Kaplan-Meir curves estimated survival between groups with 95% confidence intervals. Multivariable cox proportional hazards models adjusted for age, gender and ECOG performance status. Results: Of 683 pts, 107 received NAT and 576 underwent IR. Those in the NAT group had favourable characteristics, including younger age (mean 63 vs. 66 yrs, p < 0.01) and higher proportion of ECOG 0 vs. ≥1 (64% vs 46%) than those undergoing IR. Of those that received NAT, 64 received FOLFIRINOX and 35 nabPGem. Those receiving FOLFIRINOX were younger (mean: 60 vs. 67 yrs, p < 0.01) and were more likely ECOG 0 compared to those receiving nabPGem (72% vs. 46%, p = 0.02). Resection rates for pts undergoing IR vs. NAT were 88% vs. 50% in ER and 16% vs. 43% in BR. Rates of R0 resection margins in pts undergoing IR vs. NAT were 54% vs. 25% in ER and 6% vs. 21% in BT. Comparing ER to BR, mOS was 29.9 vs. 20.3 mths (HR: 0.54, p < 0.01). Within BR, mOS was 20.3 vs. 17.2 mths for NAT vs. IR (HR: 1.11, p = 0.74). Comparing those receiving FOLFIRINOX vs. nabPGem over all groups, mOS was 22 mths vs. 12 mths (HR: 0.31, p < 0.01). Conclusions: Real-world data confirms the use of NAT remains infrequent in this Asia-Pacific population. The use of FOLFIRINOX was associated with better survival than nabPGem based on this observational study. Improved methods for treatment selection are required. Potential biomarkers including circulating tumor DNA are being explored in the DYNAMIC-Pancreas clinical trial.

The impact of a multidisciplinary approach (MA) in the management of pancreatic disease (PD).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19196-e19196
Author(s):  
Brunella Di Stefano ◽  
Giuseppe Quero ◽  
Cinzia Bagalà ◽  
Claudio Fiorillo ◽  
Maria Bensi ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Treatment Strategy ◽  
Locally Advanced ◽  
Tumor Burden ◽  
Initial Diagnosis ◽  
Response To Treatment ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable ◽  
Border Line ◽  
The Impact

e19196 Background: The management of PD is very insidious, mainly due to the often difficult differential diagnosis between benign and malignant diseases, and, in case of pancreatic ductal adenocarcinoma (PDCA), to the frequently hard differentiation among resectable/borderline PDCA susceptible to upfront surgery, locally advanced PDCA susceptible to a neoadjuvant approach and never resectable or metastatic PDCA in which a palliative treatment is the only option. A correct PD evaluation and the subsequent choice of the most appropriate treatment strategy, thus, need a MA, involving surgeons, oncologists, radiologists, radiation oncologists, endoscopists, gastroenterologists and pathologists. On the basis of such considerations, we investigate the impact of the multidisciplinary meeting (MM) in the management of PD at our Institution. Methods: We retrospectively evaluated all the cases discussed by surgeons at our MM. We collected data, both pre- and post-MM, regarding diagnosis (cyst vs pancreatitis vs IPMN vs PDCA), and, in case of PDCA, tumor burden at baseline (resectable vs border-line resectable vs locally advanced vs metastatic disease) and disease response to treatment (disease control vs progression). Primary endpoint was the overall rate of discrepancy in diagnosis and/or PD evaluation between pre- and post-MM. Results: From October 2018 to December 2019, a total of 139 cases were presented by surgeons. After MM, a total of 38 diagnosis and/or PD evaluation were modified, for an overall discrepancy rate of 27%. In particular, of the 38 discordant cases, 9 (24%) were initial diagnosis, 24 (63%) baseline tumor burden assessments and 5 (13%) were PDCA response evaluations. Among the 24 cases of tumor burden evaluations, treatment strategy changed in 17 out of 24 cases. More specifically, of the 19 cases, evaluated as borderline/resectable before the MM, 15 were defined as locally-advanced or metastatic disease after the MM; of the 5 cases, evaluated as not resectable before the MM, 2 were considered border-line/resectable after the MM. Similarly, out of 9 cases of discrepant initial diagnosis, 5 cases, considered as malignant disease before MM, were assessed as benign after the MM. Conclusions: Our analysis demonstrates a significant rate of discrepancy in diagnosis and/or PD evaluation between pre- and post-MM. Our results show that a MA allows a considerable modification in PD diagnosis and evaluation, maximizing the treatment strategy, in particular avoiding unnecessary and detrimental pancreatic surgery.

scholarly journals Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Tiffany A. Pompa ◽  
William F. Morano ◽  
Chetan Jeurkar ◽  
Hui Li ◽  
Suganthi Soundararajan ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Splenic Vein ◽  
Advanced Pancreatic Cancer ◽  
Residual Tumor ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Celiac Artery ◽  
Ductal Adenocarcinoma ◽  
R0 Resection ◽  
Histopathological Response

Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC), the National Comprehensive Cancer Network (NCCN) suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring6.2×3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles), intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.

scholarly journals Long-Term Consequences of Exenterative Surgery for People With Pelvic Cancer

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 228s-228s
Author(s):  
J.M. Young ◽  
D. Steffens ◽  
R.L. Venchiarutti ◽  
C.E. Koh ◽  
M.J. Solomon
Keyword(s):  
Quality Of Life ◽  
Locally Advanced ◽  
Patient Reported Outcome Measures ◽  
Resection Margins ◽  
R0 Resection ◽  
Pelvic Cancer ◽  
Patient Reported ◽  
Ongoing Pain

Background: For people with recurrent or locally advanced pelvic cancer with no evidence of metastatic spread, pelvic exenteration (PE) surgery that achieves clear (R0) resection margins is the only potentially curative treatment option. This extensive, radical surgery can involve removal of the pelvic organs, muscles, nerves and bone, resulting in significant impairment for patients. Aim: The aim of this study was to describe the long-term quality of life outcomes for this procedure, specifically to investigate levels of pain, vitality and depression among survivors 3 or more years after surgery. Methods: The Royal Prince Alfred Hospital in Sydney is a national referral center for PE in Australia. Patient-reported outcome measures, including generic (SF36) and colorectal cancer-specific (FACT-C) measures of quality of life (QoL), pain, vitality and depression were assessed presurgery, every 6 months to 3 years and then annually. Consecutive patients who were 3 or more years after PE comprised the sample for this study. Trajectories for patient-reported outcomes were plotted and the proportion of survivors who experienced ongoing pain, vitality and depression at each time point were calculated. Results: Among 251 patients who were 3 years post-PE, 131 (52%, 95% CI: 46%-58%) had died and 3-year QoL assessments were completed by 69 (58%) of survivors. Three years after surgery, mean QoL scores were similar to baseline and remained fairly stable among survivors to 5 years. There was a small decrease over time in the proportion of survivors reporting ongoing pain. From 3 years onwards, ∼77% (95% CI: 67%-87%) of survivors reported ongoing pain and 44% (95% CI: 32%-56%) reported some level of depression. However, SF-36 vitality scores increased slightly from a mean of 47.2 pre-PE to 49.0 at 3 years. Conclusion: Despite the extensive nature of PE surgery, the majority of survivors achieved reasonable long-term quality of life. However, high levels of chronic pain and depression indicate ongoing needs for supportive care in this patient group.

Phase I Trial of Combined-Modality Therapy for Localized Esophageal Cancer: Escalating Doses of Continuous-Infusion Paclitaxel With Cisplatin and Concurrent Radiation Therapy

2004 ◽  
Vol 22 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Baruch Brenner ◽  
David H. Ilson ◽  
Bruce D. Minsky ◽  
Manjit S. Bains ◽  
William Tong ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Therapy ◽  
Steady State ◽  
Dose Level ◽  
Combined Modality Therapy ◽  
Locally Advanced ◽  
Radiation Therapy Oncology Group ◽  
Pathologic Complete Response ◽  
Resection Margins ◽  
R0 Resection

Purpose To define the maximum-tolerated dose (MTD) of paclitaxel when given as a weekly 96-hour infusion with cisplatin and radiotherapy for patients with esophageal cancer. Patients and Methods Thirty-four patients with locally advanced esophageal cancer and three patients with local recurrence or positive resection margins were treated. Weekly paclitaxel doses of 10, 20, 30, 40, 60, and 80 mg/m2, given as a continuous 96-hour infusion, were administered with weekly cisplatin, 30 mg/m2 on day 1, weeks 1 to 6, and concurrent radiation (50.4 Gy). Plasma paclitaxel steady-state levels were measured. Results Dose-limiting toxicity, defined as a treatment break longer than 2 weeks for toxicity, occurred in one patient in the 80-mg/m2/wk dose level. Major causes for any (including ≤ 2 weeks) treatment breaks were mediport complications and neutropenic fever, which occurred mostly at that dose level. At a paclitaxel dose of 60 mg/m2/wk, myelosuppression, mostly neutropenia, was relatively mild and transient; stomatitis, esophagitis, diarrhea. and peripheral neuropathy were uncommon and usually of grade 2 or less. Therefore, the MTD was established at 60 mg/m2/wk. The mean steady-state concentration of paclitaxel at the MTD was 17.2 nmol/L. Complete (R0) resection was possible in 16 (73%) of 22 patients who underwent subsequent surgery, and the pathologic complete response rate was 24%. Conclusion Weekly, 96-hour infusion of paclitaxel 60 mg/m2/wk, given with concurrent cisplatin and radiotherapy, is a safe and tolerable regimen for patients with localized esophageal cancer. Preliminary efficacy data are encouraging. This regimen is the basis of ongoing Radiation Therapy Oncology Group phase II randomized trials in esophageal and gastric cancers.

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