Clinical Investigation
Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

Presented in part at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, January 25th 2013, San Francisco, CA; and at the Society of Surgical Oncology 66th Annual Cancer Symposium, March 7th 2013, Washington DC.
https://doi.org/10.1016/j.ijrobp.2014.05.053Get rights and content

Purpose

To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma.

Methods and Materials

Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference.

Results

Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit.

Conclusions

The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical resection, most domains returned back to baseline levels by 6 months.

Introduction

Approximately 20% to 30% of patients who undergo pancreatectomy for pancreatic adenocarcinoma do not receive adjuvant therapy, often owing to slow recovery after surgery. Although adjuvant chemotherapy and/or radiation therapy has been shown to improve local recurrence and survival, it is associated with treatment-related morbidity and mortality 1, 2, 3, 4. Neoadjuvant therapy increases the likelihood that patients will receive chemotherapy and radiation, without incurring delays resulting from postoperative recovery. Further, the potential for therapy-related downstaging of the primary tumor might allow higher rates of margin-negative resection, a particularly important issue in borderline resectable cases (5). Specific benefits for the incorporation of neoadjuvant radiation therapy include the ability to treat with smaller radiation therapy volumes, thus limiting toxicity. By limiting toxicity, neoadjuvant radiation therapy can be delivered concurrently with full-dose chemotherapy 6, 7.

The impact of neoadjuvant chemoradiation on the quality of life (QOL) of patients with pancreatic cancer is not known, because prospective QOL data in this patient population are limited. Given the short life expectancy of these patients and the high potential for treatment-related toxicity, it is important to understand how QOL can be affected during and after completion of neoadjuvant treatment. Preservation of function and well-being in everyday life has become a key component of the health care goals for cancer patients 8, 9. This is especially important in the neoadjuvant setting, where deterioration of health-related QOL and performance status may impact patients' ability to tolerate a major pancreatectomy. The working hypothesis of this study was that global QOL did not decrease from baseline to re-evaluation after 2 cycles of neoadjuvant chemoradiation.

Section snippets

Study design

This was a substudy of a prospective, multi-institutional, phase 2 trial (10). Patients with untreated pancreatic adenocarcinoma consented to receive neoadjuvant chemoradiation with full-dose gemcitabine and oxaliplatin, with accrual occurring between July 2007 and February 2010. Eligible participants were required to have pathologic confirmation of pancreatic adenocarcinoma and resectable or borderline resectable staging according to the National Comprehensive Cancer Network guidelines (11).

Patient description

There were 71 participants enrolled onto the clinical trial. The QOL component of this study was started after 7 participants were already included into the trial. Of 64 potential participants eligible for QOL, 57 completed at least 1 QOL instrument, and 55 were included in the final analysis (Fig. 1). All further references below relate to these 55 participants.

There were 29 men and 26 women, median age 64 (range, 42-82) years. At diagnosis, 36 of 55 patients (65%) had borderline resectable

Discussion

There is limited literature evaluating the impact of neoadjuvant therapy on QOL in pancreatic cancer (16). This prospective analysis examined the QOL outcomes of patients with pancreatic adenocarcinoma who received neoadjuvant full-dose gemcitabine and oxaliplatin with concomitant conformal radiation, followed by surgery and 2 postoperative cycles of chemotherapy (10). Our results indicate that although this neoadjuvant treatment protocol is associated with an initial decrease in global

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    This research is supported (in part) by the National Institutes of Health through the University of Michigan's Cancer Center Support Grant (5 P30 CA46592) by the use of the Cancer Center Clinical Trials Office and Biostatistics Core and (in part) by Sanofi.

    Conflict of interest: M.M.Z. received research support from Sanofi for his reported clinical trial. T.S.B.-S. receives support from Sanofi as a consultant. A.C.W. has received honoraria from Sanofi.

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