# Presentation: 673530

## NCI Clinical Announcement

- Intraperitoneal chemotherapy for women with ovarian cancer
- Edward L. Trimble, MD, MPH

## History

- Dedrick R, Myers C, Bungay P et al. PK rationale for peritoneal drug administration in the treatment of ovarian cancer. _Cancer Treat Rep_ 1978
- High IP drug concentration
- Prolonged IP drug half-life
- Prolonged systemic drug half-life

## Early lessons from clinical trials

- IP chemotherapy ineffective for women with bulky intra-abdominal disease
- PK advantages high for certain drugs (IP vs IV)
- 10-20-fold: cisplatin, carbioplatin
- >1000: paclitxel, docetaxel

## Phase III evaluation

- US, Europe, Taiwan
- Six trials for women with advanced stage ovarian cancer after primary surgery
- One consolidation trial for women NED after primary surgery and chemotherapy

## NCI sponsored phase IIII trials 

- SWOG 8501/ GOG 104
- Accrual: 1988-1992
- Cisplatin/ cyclophosphamide IV vs cisplatin IP/ cyclophosphamide IV
- NEJM 1996: Alberts et al
- GOG 114/ SWOG 9227/ECOG
- Accrual: 1992-1993
- Cisplatin IV/ paclitaxel IV vs carboplatin x 2 + cisplatin IP/ paclitaxel IV
- JCO 2001: Markman et al

## NCI-sponsored phase III trials

- GOG 172
- Accrual: 1998-2001
- Cisplatin/ paclitaxel IV vs cisplatin IP/ paclitaxel IV+IP
- NEJM 2006: Armstrong et al

## <footer>

- <date/time>

******2**** ****heterogeneity (3 d.f.)****= 0.629, p=0.89**
**The red diamond shows the pooled estimate of the treatment hazard ratio for PFS: 0.79, 95% confidence interval (0.70, 0.90).**
**PFS hazard ratios are not available from the published report on SWOG-8501/ GOG 104 or th study of Yen et al.**
**PFS hazard ratio is not reported for the study of Gadducci et al but it is calculated from the available data reported.**

- <date/time>

******2**** ****heterogeneity (5 d.f.)****= 3.1, p=0.68**
**Hazard ratio is not reported for the GONO study but it is calculated from the available data reported.**
**Hazard ratio is not reported for the Greek study.**

## NCI Clinical Announcement

- “To bring new information of unusual importance  to the attention of clinicians as rapidly as possible”
- Review of data by independent panel, nominated by investigators and NCI
- Recommendation forwarded to NCI Director
- Timed with publication of data

## NCI Clinical Announcements

- Adjuvant therapy, node- breast cancer, 1988
- Levamisole & 5FU, Dukes C colon cancer, 1989
- Adjuvant therapy, rectal cancer, 1991
- Adjuvant therapy, breast cancer, tamoxifen update, 1995
- Chemoradiation for cervical cancer, 1999

## Process for IP Clinical Announcement

- Proposed by GOG and SWOG investigators
- Independent panel of gyn oncs, med oncs, patient advocates, biostatisticians nominated by GOG, SWOG, EORTC, and NCI
- Panel reviewed data and voted to recommend that NCI issue a clinical announcement

## Process for IP Clinical Announcement

- Proposal for clinical announcement reviewed by NCI SMT and  EC
- Review of SEER and SEER/Medicare data showed <1% of women with stage III ovarian cancer received IP chemotherapy
- Focus groups of MDs, advocates, nurses

## Top ten reasons not to give IP chemo

- 10. I don’t believe the data.
- 9. I don’t know how to give IP chemo.
- 8. I don’t like to use cisplatin anymore.
- 7. There is no standard IP regimen.
- 6. It takes longer than IV chemo.

## Top ten reasons not to give IP chemo (cont’d)

- 5. Giving IV carbo/ paclitaxel is so easy.
- 4. IP chemo has more toxicity.
- 3. There’s no drug rep pushing IP chemo.
- 2. It’s an old idea.
- 1. It requires optimal surgical cytoreduction and a IP port.

## Process for IP Clinical Announcement

- Development of trans-NCI team
- Review of text of announcement
-  NIH, FDA, independent panel
- BMS as co-sponsor of SWOG 8501 and GOG 114

## NCI IP Clinical Announcement Team

- Office of the Director
- Offices of Communication, Education & Special Initiatives, Liaison Activities, Women’s Health
- Division of Cancer Control and Population Sciences
- Division of Cancer Prevention
- Division of Cancer Treatment and Diagnosis

## Dissemination: publication

- Primary endpoint of GOG 172
- Armstrong et al, _NEJM_ 2006 (expedited)
- Cannistra (editorial), _NEJM_ 2006
- Secondary endpoint of GOG 172
- IP catheter outcomes
- Walker et al, _Gynecologic Oncology_ 2006 (expedited, simultaneous electronic release)
- Trimble & Christian (editorial), _Gynecologic Oncology_ 2006
- Review articles
- Green, _Lancet_ (in press)

## Dissemination: press

- Joint national release
- Timed with NEJM publication
- NCI, GOG, Society of Gynecologic Oncologists, Gynecologic Cancer Foundation, Oncology Nursing Society, Society of Gynecologic Nurse Oncologists
- Local press releases
- NCI Cancer Centers and research sites active in IP trials

## National TV coverage

- ABC: Good Morning America, World News Tonight, 17 local affiliates
- NBC News Channel->affiliates
- 14 Fox affiliates
- CBS:  Morning News, 3 affiliates

## National wire services

- Associated Press
- Reuters
- United Press International

## National Newspaper Coverage

- USA Today
- New York Times (Jan 5 & 17)
- Boston Globe
- Los Angeles Times (Jan 5 & 23)
- Newsday
- Baltimore Sun

## Local newspapers

- Seattle Post-Intelligencer, p. 1
- Columbus (Ohio) Dispatch, p. 1
- Daily Oklahoman, p. 1
- Raleigh News & Observer, p. 1
- Worcester (Mass) Telegram & Gazette, p. 1
- Cleveland Plain Dealer, p. 1

## Foreign press

- Agence France
- The Australian, Perth Sunday Times
- UK Daily Mail
- Toronto Star, Montreal Gazette, Edmonton Journal

## Dissemination: advocacy groups

- Conference call organized by NCI OLA
- Day of NEJM and IP Clinical Announcement release
- Ovarian cancer advocacy groups in US, Canada, and UK
- Newsletters, websites, broadcast emails, presentations at annual meetings

## Dissemination : web and CIS

- NCI home page
- NCI digest page on ovarian cancer
- Joint press release, FAQs
- 9,779 page views

## Dissemination: web and CIS

- PDFs of NEJM article and Clinical  Announcement
- PDQ
- Listing of centers with expertise in ovarian cancer
- Multidisciplinary, surgical cytoreduction, IP chemotherapy, clinical trials

## Dissemination: web and GOG

- Educational material for doctors and nurses
- How to place an IP port, how to give IP therapy, how to manage toxicities
- Patient educational materials

## Dissemination

- Professional societies
- ASCO, ACOG, ACOS, ONS, SGO, SGNO, SSO
- Cooperative Groups
- Local, regional and national conferences
- Australia, Austria, Canada, UK

## Plans for Evaluation

- Early adopters: NCCN, Cancer Research Network
- Later adopters: SEER 2006 Patterns of Care, SEER-Medicare, National Cancer Data Base
- Industry: IP port sales, pharmaceutical sales