Controversies in adjuvant therapy for pancreatic cancer
This presentation is the property of its rightful owner.
Sponsored Links
1 / 29

Controversies in Adjuvant Therapy for Pancreatic Cancer PowerPoint PPT Presentation


  • 121 Views
  • Uploaded on
  • Presentation posted in: General

Controversies in Adjuvant Therapy for Pancreatic Cancer. Parag Sanghvi M.D. Tasha McDonald M.D. Department of Radiation Medicine OHSU. Median Survival of Patients With Pancreatic Cancer. Localized/ Resectable15-19 months 10% Locally Advanced 6-10 months 30%

Download Presentation

Controversies in Adjuvant Therapy for Pancreatic Cancer

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Controversies in Adjuvant Therapy for Pancreatic Cancer

Parag Sanghvi M.D.

Tasha McDonald M.D.

Department of Radiation Medicine

OHSU


Median Survival of Patients With Pancreatic Cancer

  • Localized/ Resectable15-19 months 10%

  • Locally Advanced 6-10 months 30%

  • Metastatic/ Advanced 3-6 months 60%


Adjuvant Therapy

  • No clear consensus on adjuvant therapy for pancreatic cancer

    • Difference in philosophy between Europe & North America

  • Europeans have moved to adjuvant chemotherapy alone


Adjuvant ChemoRT


GITSG (1985)

  • 43 pts randomized into two groups

  • XRT/bolus 5-FU  5FU X 2 years vs. Observation

  • Split course radiation – total dose 40 Gy

  • Median survival – 20 vs. 11 months

  • 2 y OS – 43% vs. 18%


EORTC (1999)

  • Phase III randomized trial

  • Adjuvant chemoRT vs. observation

  • Split course RT (40 Gy) with concurrent 5 FU vs. Observation

  • Median survival 24.5 months vs. 19.0 months (p = 0.21)

  • 2 y OS 41% vs. 51% (p = 0.21)


EORTC (1999)


EORTC (1999)

  • Criticism is that this study included patients with ampullary tumors

  • Improved benefit of adjuvant therapy seen in patients with pancreatic head tumors

    • 2 y OS 34 % vs. 26% (p = 0.099)

    • MS 17.1 months vs. 12.6 months


ESPAC 1 (2001)

  • Randomized trial with 2 X 2 factorial design

  • Patients randomized to

    • Chemoradiation

    • Chemoradiation followed by Chemotherapy

    • Chemotherapy alone

    • Observation

  • Radiation was split course RT (total dose 40Gy; 2 week course)

  • Chemotherapy was 5FU + Leucovorin


ESPAC 1 (2001)


ESPAC 1 (2001)ChemoRT vs. No ChemoRT

  • MS 15.9 months vs. 17.9 months

  • 2 y OS 29% vs. 41% (p = 0.05)


ESPAC 1 (2001)Chemotherapy vs. No Chemotherapy

  • MS 20.1 vs. 15.5 months (p = 0.009)

  • 2 y OS 40% vs. 30%


ESPAC 1 (2001)Criticisms

  • Split course RT; No central review of RT

  • Doses ranged from 40-60 Gy; treatment not uniform or not delivered in 30% patients

  • Significant protocol violations in all arms; cross-over allowed


Newer Trials

  • CONKO -001 (2007)

    • Adjuvant chemotherapy vs. observation

  • RTOG 9704 (ASCO 2006)


CONKO-001 (2007)Oettle et al. (JAMA)

  • Randomized Phase III European trial; 368 patients

  • T1-4 N0-1 M0 pancreatic cancer

  • R0 or R1 resection

  • Chemotherapy

    • Started 10-42 d after surgery

    • 6 cycles of Gemcitabine q 4 weeks

    • Each cycle – 3 weekly infusions 1000mg/m2


CONKO-001 (2007)

  • Results

    • Median DFS 13.4 months vs. 6.9 months (p < 0.001)

      • R0 13.1 months vs. 7.3 months

      • R1 15.8 months vs. 5.5 months

    • OS MS 22.1 vs. 20.2 months (p = 0.06)

    • Overall, 83% of all patients had relapses


CONKO-001 (2007)


RTOG 9704 (ASCO 2006)

  • 538 patients enrolled; 442 eligible & analyzable

  • T1-T4 N0-1 M0

  • 381 pancreatic head lesions

  • Patients randomized to pre and post chemoRT 5FU vs. pre and post chemoRT gemcitabine


RTOG 9704Treatment Paradigm


RTOG 9704 Results

  • No statistically significant difference in OS between the two arms when all patients analyzed

  • However, patients with pancreatic head lesions showed significantly improved survival in the Gemcitabine arm

    • MS 36.9 months vs. 20.6 months

    • 3 y OS 32% vs. 21%


RTOG 9704Results


RTOG 9704Results

  • No real gains in survival seen in this 1st RCT with modern doses / treatment technique compared to historical RCT with split course lower dose RT


Adjuvant Radiation Therapy in Surgically Resected Pancreatic Cancer: SEER Database

  • 1973 - 2003

  • 2636 patients with resectable pancreatic cancer

    • 1123 received adjuvant RT

    • 1513 did not receive any adjuvant therapy

  • Median F/U 19 months


Adjuvant Radiation Therapy in Surgically Resected Pancreatic Cancer: SEER Database

  • Median Survival

    • Adjuvant RT vs. No RT – 18 months vs. 11 months (p <0.001)

  • Cox regression showed HR 0.57 (0.52,0.63; p<0.01)

  • Independent statistically significant factors linked to decreased survival

    • African Americans

    • Moderate & Poorly diff. adenoCA

    • Age <60

    • Stage


Mayo Clinic Experience

  • Retrospective review of 472 consecutively treated patients with R0 resection

  • T1-3 N0-1 M0

  • 1975-2005

  • If adjuvant chemoRT given

    • Median dose 50.4 Gy

    • 98% received concurrent 5FU based chemotherapy


Mayo Clinic ExperienceResults


Mayo Clinic ExperienceResults


Future Trials – ESPAC 3


Conclusions

  • Obvious controversies in management of pancreatic cancer

  • All randomized trials have significant flaws

  • What we need (but will not get) is a well designed RCT

    • Our design: 3 arms, no cross-over

      • Observation

      • Adjuvant chemotherapy (gemcitabine)

      • Adjuvant chemoRT (5-FU with RT to 50.4 Gy followed by gemcitabine)


  • Login