Journal of Clinical Oncology
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`The Ofificial Journal of the American Society of Clinical Oncology
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`Vol 16, No 3
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`March 1998
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`CONTENTS
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`EDITORIAL; What Is the Role for Adjuvant Radiation Therapy in Advanced Hodgkin’s Disease?
`Peter Mauch
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`RAPID PUBLICATION
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`Meta-Analysis of Chemotherapy Versus Combined Modality Treatment Trials in Hodgkin’s Disease
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`M. Loefiler 0. Brosteanu, D. Hasenclever, M. Sextro, D. Assouline, A.A. Bartolucci, P.A. Cassileth, D. Crowther,
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`V Diehl, R.I. Fisher, RT Hoppe, R Jacobs, J.L. Pater, S. Pavlovsky, E. Thompson, and R Wiernik for the
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`International Database on Hodgkin’s Disease Overview Study Group
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`ORIGINAL REPORTS
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`Hematologic Oncology
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`Influence of More Extensive Radiotherapy and Adjuvant Chemotherapy on Long-Term Outcome of
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`Early-Stage Hodgkin’s Disease: A Meta-Analysis of 23 Randomized Trials Involving 3,888 Patients
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`L. Specht, R. G. Gray, M.J. Clarke, and R. Peto for the International Hodgkin’s Disease Collaborative Group
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`Effect of Follicularity on Autologous Transplantation for Large-Cell Non-Hodgkin’s Lymphoma
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`Julie M. Vose, Philip J. Bierman, James C. Lynch, Dennis D. Weisenburger, Anne Kessinger Wing C. Chan,
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`Timothy C. Greinet; and James 0. Armitage
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`Fewer Infections, but Maintained Antitumor Activity With Lower-Dose Versus Standard-Dose Cladribine in
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`Pretreated Low-Grade Non-Hodgkin’s Lymphoma ..................... ..D. C. Betticher, A. von Rohr, D. Ratschiller,
`S.-F Hsu Schmitz, T Egger, T. Soncleregger, R. Herrmann, 7". Kroner G.B. Zulian, F Cavalli, M.F Fey,
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`and T. Cerny
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`Long-Term Survival in Primary CNS Lymphoma ..... ..Lauren E. Abrey, Lisa M. De/lngelis, and Joachim Yahalom
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`I-Iigh-Dose Methotrexate for the Treatment of Primary Cerebral Lymphomas: Analysis of Survival and Late
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`Neurologic Toxicity in a Retrospective Series ................ . Jean-Yves Blay, Thierry Conroy, Christine Chevreau,
`Antoine Thyss, Nathalie Quesnel, Houchingue Eghbali, Reda Bouabclallah, Bertrand Coiffter,
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`Jean—Philippe Wagner Annick Le Mevel, Dominique Dramais-Marcel, Elisabeth Baumelou, Frank Chauvin,
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`and Pierre Biron
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`Journal of Clinical Oncology (ISSN 0732-183X) is published monthly by W.B. Saunders Company. ‘Corporate and Editorial Offices: The Curtis
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`Center, Independence Square West, Philadelphia, PA 19106-3399. Accounting and Circulation Offices: WB. Saunders Company, 6277 Sea Harbor Dr,
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`Orlando, FL 32887-4800. Periodicals postage paid at Orlando, FL 32862, and at additional mailing offices.
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`Editorial correspondence should be addressed to George P. Canellos, MD, Journal of Clinical Oncology, 850 Boylston St, Suite 301A, Chestnut
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`Hill, MA 02167. Telephone: (617) 739-8909. Fax (617) 739-8541. Email: whippend@asco.org. Internet: http://www.jcojournalorgl
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`POSTMASTER: Send change of address to Journal of Clinical Oncology, c/0 W.B. Saunders Company, 6277 Sea Harbor Dr, Orlando, FL
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`32887-4800.
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`Yearly subscription rates: United States and possessions: individual, $247.00; institution, $317.00; single issues, $30.00. All other countries:
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`individual, $330.00; institution, $386.00; single issue, $30.00. Student and resident: United States and possessions: $83.00, all other countries:
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`$104.00. To receive student/resident rate, orders must be accompanied by name of affiliated institution, date of term, and the signature of
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`program/residency coordinator on institution letterhead. Orders will be billed at individual rate until proof of status is received. Current prices are in
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`effect for back volumes and back issues. Back issues sold in conjunction with a subscription rate are on a prorated basis. Subscriptions are accepted on
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`a calendar year basis. Prices are subject to change without notice. Single issues, both current and back, exist in limited quantities and are offered for
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`sale subject to availability.
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`Pae2of7
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`PTX-218.0002
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`Page 2 of 7
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`Use of,Dexamethasone and Granisetron in the Control
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`of Delayed Emesis for Patients Who Receive Highly
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`Emetogenic Chemotherapy
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`By Jean Latreille, Joseph Pater, Dianne Johnston, Francis Laloerge, David Stewart, James Rusthoven, Paul Hoskins,
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`Brian Findlay, Elissa McMurtrie, Louise Yelle, Christopher Williams, David Walde, Scott Ernst, Horhhaian Dhaliwal,
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`David Warr, Frances Shepherd, David Mee, Laurie Nishimura, David Osoba, and Benny Zee For the National Cancer
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`Institute oi Canada Clinical Trials Group
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`(216 patients). All patients completed diaries in which
`episodes of emesis and severity of nausea were re-
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`corded.
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`Results: The addition of granisetron on days 2
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`through 7 had no discernable impact on nausea and
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`vomiting during this period.
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`Conclusion: The administration of a 5-hydroxytryp-
`taminea, receptor (5-HT3) antagonist, in this case granis-
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`etron, after 24 hours conferred no benefit. This negative
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`result needs to be assessed in light of conflicting litera-
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`ture, but at present it does not appear that the routine
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`use of these drugs in this setting is iustified.
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`J Clin Oncol 16:1 174-1 178. © 1998 by American
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`Society of Clinical Oncology.
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`Purpos : To evaluate the roles of granisetron and
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`dexamethasone for emesis control on days 2 through 7
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`after the administration of cisplatin in doses of 50
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`mg/m‘ or greater to patients who had not previously
`received chemotherapy.
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`Patients am_l_Methods: Four hundred thirty-five eli-
`gible and assessable patients were randomized to one
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`of two arms in a double-blind fashion: arm A; granis-
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`etron 3 mg intravenous (IV) plus dexamethasone 10 mg
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`IV prechemotherapy followed by granisetron 1 mg
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`orally at 6 and 12 hours, then granisetron 1 mg orally
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`and dexamethasone 8 mg orally twice daily on days 2
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`through 7 (219 patients); arm B; as in arm A but with
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`placebo substituted for granisetron on days 2 through 7
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`5-HYDROXYTRYPTAMINE3 receptor (5-HT3) antago-
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`nists are clearly established as effective agents in the
`management of nausea and vomiting induced by cancer
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`chemotherapy,‘ and they are now used routinely to control
`emesis in the 24 hours after the administration of highly
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`emetogenic drugs, such as cisplatin. However, it is uncertain
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`whether there is any benefit to continue their administration
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`after 24 hours to prevent the development, or reduce the
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`frequency, of delayed nausea and vomiting. There are only
`limited data from randomized trials that address the question
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`Front the Hotel-Dieu de Montreal Hospital; Hépital Notre-Dame, Mon-
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`tréol; Hopitol Iovol, Ste-Foy; Ottawa Regional Cancer Center; Ottawa;
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`Hamilton Regional Cancer Center, Hamilton; British Columbia Cancer
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`Agency, Vancouver Centre, Vancouver,‘ Hotel-Dieu Hospital, St. Catharines;
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`British Columbia Cancer Agency, Vancouver Island Centre, Wctoria; Allan
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`Blair Cancer’ Centre, Regina; Algoma District Health Centre, Soult Ste
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`Marie; Tom Baker Cancer Centre, Calgary: Thunder Bay Regional Cancer
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`Centre, Thunder Bay; Princess Margaret Hospital; Toronto General Hospi-
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`tal, Toronto; SmithKline Beecham Phamut Inc, Oakville; and the Clinical
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`Trials Group, Kingston, Canada.
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`Submitted Decetnber 4, 1996; accepted October 7, I997.
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`Supported in part by SmithKline Beecham Pharmo Inc, Oakville; and
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`a grant from the National Cancer Institute of Canada; Kingston,
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`Canada.
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`Address reprint requests to Jean Latreille, MD, Hotel-Dieu de Montreal
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`Hospital, Haematology-oncology Division, 3840 Saint-Urbain St, Montréal,
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`Quebec, Canada, H2WI T8; Emailjlatrei@cam.0rg.
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`© 1998 byAmerican Society of Clinical Oncology.
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`0732-] 83X/98/I 603-00]5$3. 00/0
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`of maintenance (beyond 24 hours) antiemetics in patients
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`who receive cisplatin. Both steroids alone and the co1nbina—
`tion of steroids and metoclopramide have been found to
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`reduce delayed emesis in these patients.” Despite these
`results, most studies of 5-HT3 antagonists in this context
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`have used placebo controls. One such trial found a nonsignifi—
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`cant difference in favor of continued ondansetron therapy,4
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`whereas a more recent study showed a statistically signifi-
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`cant advantage of this drug over placebo.5 In a recent tpial,
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`the Italian Group for Aiitiemetic Research compared contin-
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`ued ondansetron and dexamethasone to metoclopramide and
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`deXamethasone.6 There were no statistically significant
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`differences overall, but there appeared to be an advantage to
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`ondansetron in patients who vomited in the first 24 hours.
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`This study was designed to address the following ques-
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`tion: Does the continuation of granisetron improve control
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`of emesis in the 6 days compared after administration of
`emetogenic drugs with dexamethasone alone?
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`PATIENTS AND METHODS
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`I
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`Overall Design
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`The two arms of this trial were: arm A, granisetron and dexa1netha-
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`sone for 7 days; and arm B, granisetron and dexamethasone on day 1
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`followed by dexamethasone and placebo on days 2 through 7. A third
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`arm, granisetron alone, was included during the earlier phases of the
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`trial to assess the effect of adding dexamethasone to granisetron. Results
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`of that component of the trial have already been reported.7
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`H74
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`Journal of Clinical Oncology, Vol i6, No 3 (March), 1998: pp 1 174-1 178
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`Pae3of7
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`PTX-218.0003
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`Page 3 of 7
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`DELAYED EMESIS AFTER HIGH-DOSE CISPLATIN
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`H75
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`Eligibility
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`All patients received cisplatin 50 mg/m2 or greater as their first-ever
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`chemotherapy, were 18 years of age or older, had a World Health
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`Organization (WHO) performance status of 2 or less (< 50% of the
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`normal day spent in bed), gave written informed consent, and were
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`under the care of a participating investigator.
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`The exclusion criteria included liver function tests (AST, ALT)
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`greater than 4 times the upper normal
`limit; contraindication to
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`cisplatin, such as renal dysfunction; congestive cardiac failure New
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`York Heart Association (NYHA) classification grades IH or IV; acute
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`nausea and/or vomiting within 48 hours before randomization; a history
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`of chronic nausea and/or vomiting; use of antiemetic drugs within 7
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`days before randomization; contraindication to dexamethasone either
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`from active peptic ulcer disease or uncontrolled diabetes mellitus;
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`gastric compression or subaeute bowel obstruction; life expectancy of
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`less than 3 months; a generalized or partial seizure within the last year;
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`primary or secondary brain tumors; any medication with CNS effects
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`(except short-acting benzodiazepines or morphine analogs) that re-
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`quired one or more close changes during the week before randomization;
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`administration of corticosteroids other than dexamethasone during the
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`study period; concomitant radiotherapy to the abdomen during the
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`period of assessment; any other investigational new drug during the 3
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`months before treatment or during treatment; unwillingness or inability
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`to comply with the protocol or an inability to complete the quality-of-
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`life questionnaires or diary; and lactose intolerance (lactose was added
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`to the capsules containing granisetron and dexamethasone as a filler).
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`Treatment Allocation
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`Patients were registered centrally. Randomization was by a computer-
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`generated series of random numbers and stratification was by cisplatin
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`dose (50 to 74 mg/m2, 2 75 mg/m2). Pharmacists in the treating centers
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`were blinded, as were the doctors, nurses, and patients.
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`Pretreatment Assessment
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`Screening evaluations took place within 7 days before randomization
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`and included a complete medical history, physical examination, and
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`laboratory investigations. All patients completed a quality-of-life ques-
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`tionnaire. The questionnaire used was the QLQ-C30 developed by the
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`Quality of Life Study Group of the European Organization for Research
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`and Treatment of Cancer.8 This instrument assesses global quality of
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`life, five functioning domains, and nine symptom categories. Patients
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`also completed a diary that included questions about nausea, the number
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`of vomiting episodes and food intake during the previous 24 hours, and
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`a visual analog scale (VAS) to measure nausea severity and duration,
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`anxiety, and drowsiness during the same baseline period.
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`Treatment Administration
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`Patients were admitted to the hospital for cisplatin administration and
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`kept for a 12-hour observation period. Thirty-five minutes before the
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`cisplatin infusion, patients received dexamethasone 10 mg intravenous
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`(IV) over 15 minutes. Twenty minutes before cisplatin administration
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`patients received granisetron 3 mg IV infused over 15 minutes.
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`Cisplatin was administered as a single 3-hour infusion (mininum 1 hour,
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`maximum 6 hours). Additional emetogenic chemotherapy (such as
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`doxorubicin, cyclophosphamide, vinblastine) was allowed on day 1
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`only after the cisplatin infusion. If patients were to receive a multiday
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`regimen, only bleomycin, fluorouracil, vinca alkaloids, etoposide, or
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`methotrexate were allowed on days 2 through 7. No other highly or
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`moderately emetogenic chemotherapy was allowed after day 1. Six and
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`12 hours after beginning cisplatin, patients were given granisetron 1 mg
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`Pae4of7
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`orally. At 24 hours, patients on arm A received granisetron 1 mg orally
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`and dexamethasone 8 mg orally twice a day for 6 days, whereas patients
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`on arm B received dexamethasone 8 mg orally and placebo twice a day
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`for 6 days. To ensure that all medical staff and patients remained blinded
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`throughout
`the study, both IV and oral matching placebos were
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`provided.
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`Evaluation Criteria
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`Patients completed a diary every 6 hours for the first 24-hour period
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`and then each day for the remaining 6 days. The increased frequency of
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`diary completion in the first 20 hours was undertaken to support the
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`component of this study already reported, io, the assessment of the
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`impact of the addition of dexamethasone to granisetron in the control of
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`— acute nausea and vomiting.7 These diaries consisted of a categoric scale
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`regarding nausea (none, mild, moderate, severe), number of episodes of
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`vomiting (1, 2, 3, 4, > 4), and food intake (much better, better, same as
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`last week, worse, much worse). In addition, 100 nnm VAS for nausea
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`duration (none of the time, all of the time), nausea severity (no nausea,
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`extremely severe nausea), drowsiness (never drowsy, constantly drowsy),
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`and anxiety (none, severe) were completed. The scales were oriented so
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`that 0 mm indicated no nausea (or anxiety, etc) and 100 mm indicated
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`the worst possible nausea (or anxiety, etc). Twelve hours from the start
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`of chemotherapy, the patients were asked if rescue medications had
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`been used for breakthrough symptoms of nausea or vomiting and if they
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`felt different in any way since starting treatment. Vital signs were
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`recorded at 6 and 12 hours after the beginning of chemotherapy.
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`One week after cisplatin therapy, patients returned to the clinic and
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`their medication packs, which contained any unused capsules, and
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`diaries were checked for compliance. At that time, they completed the
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`QLQ-C30 questionnaire, had vital signs, blood and urine samples taken
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`and were asked about the use of any rescue medications and adverse
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`events. The patients were seen again before their next cycle of
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`chemotherapy (days l5‘through 29), when the follow-up procedures and
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`tests were again completed.
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`Statistical Methods
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`The protocol-specified primary end points for the analysis included
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`the following: total control of emesis (TCE), defined as no vomiting, no
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`nausea, no rescue medication, and no missing data during the 7-day
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`period; complete control of emesis (CCE), defined as no vomiting, no
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`worse than mild nausea, no rescue medication, and no missing data
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`during the 7-day period; Vomiting control (VC), defined as no vomiting,
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`no rescue medication, and no missing data; and nausea control (NC),
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`defined as no nausea, no rescue medication, and no missing data.
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`Nausea severity scores were averaged over the 7 days and reported as
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`mean nausea severity.
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`The chi-square statistic was used to test the significance of differ-
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`ences between the groups during the 7-day period. Patients with missing
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`data for any time period were handled in two ways in these univariate
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`analyses: (1) The patient was considered to have experienced treatment
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`failure at the point in time for which the data were missing or (2) the
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`missing data were ignored and the patient was not considered to have
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`treatment failure until positive evidence of failure was recorded. The
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`results of the comparisons between arms were the same whichever
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`method was used, although the more conservative approach that
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`considered missing data to represent treatment failure produced lower
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`overall control rates. For simplicity, only the “missing as failure"
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`results are presented here. 'A logistic regression was used to assess and
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`control for the effects of important prognostic factors. The average
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`severity of nausea, drowsiness, and anxiety were analyzed using the
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`Wilcoxon rank-sum test. The multiple linear regression method was
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`PTX-218.0004
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`Page 4 of 7
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`

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`H76
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`used to assess and control for the effects of important prognostic factors
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`for nausea as measured by the VAS. The average VAS score for each
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`individual over 24 hours and 7 days was calculated if more than 50% of
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`the information of that item was in the patient’s diary. If the item had
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`50% or more missing data, that specific VAS outcome was excluded
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`from the analysis. For the regression analysis, patients with missing data
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`for either the outcome or the prognostic factors were excluded from the
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`analysis.
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`The time to event data were analyzed using the Kaplan—Meier
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`estimates, and a log-rank test was used to compare the difference
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`between the two treatment groups. Patients were supposed to record
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`both the number of emetic episodes and the time of the first episode in
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`the diary. Occasionally, the time of first emesis was inconsistent with the
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`interval in which emesis was first recorded. In such cases, the earlier
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`event was taken as a conservative estimate of the time of first event. If
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`the time of emetic episode was not reported, the midpoint of the interval
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`was used in the time to event analysis. Because the definition of lack of
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`control of emesis included any additional antiemetic treatment, addi-
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`tional antiemetic treatment without a date was considered to have
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`happened at the first 6-hourly period. Patients who had a date of
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`additional antiemetic use but ‘did not specify the time were considered to
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`have taken the additional antiemetic at the beginning of the day.
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`Administrative Data
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`RESULTS
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`A total of 447 patients were randomized between April
`1991 and June»1994 from 21 centers across Canada, and all
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`centers obtained their research ethics board approval. Ten
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`patients were ineligible and two were unassessable. Of the
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`10 ineligible patients, five received contraindicated medica-
`tion before treatment and five had nausea and vomiting
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`before treatment at baseline. Two patients became unassess-
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`ablc after randomization: one developed abnormal liver
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`function and the other received carboplatin instead of
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`cisplatin. Of the 435 eligible and assessable patients, one did
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`not complete the diary. This patient died of disease progres-
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`sion within 30 days of randomization and the diary was not
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`returned by the family. Adequate information about the
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`efficacy of the antiemetic therapy was recovered from the
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`case report form.
`The proportion of patients considered to have treatment
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`failure because of missing data are 2.3%, 4.6%, 5.3%, and
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`2.3% for TCE, CCE, VC, and NC, respectively. As previ-
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`ously explained, comparative results were the same regard-
`less of whether missing data were excluded.
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`Of the 435 assessable and eligible patients, 219 received
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`granisetron plusdexamethasone (arm A) and 216 received
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`dexamethasone only (aim B).
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`Pretreatment Patient Characteristics
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`Baseline characteristics of the patients in the two study
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`groups are listed in Table 1. The majority were women
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`between the ages of 45 to 65 years, had a WHO performance
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`Pae5of7
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`Table l. Baseline Characteristics
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`Arm A
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`in = 219)
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`58
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`57/43
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`3.55
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`88
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`Mean age, years
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`Female/male, %
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`Alcohol consumption, drinks/day
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`Perlormance status, S l, %
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`Cisplotin, %
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`50-74 mg/m2
`2 75 mg/ml
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`Cisplatin dose, mean
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`Disease site, %
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`Lung
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`Ovary
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`Head and neck
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`Other
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`Motion sickness, %
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`Metastatic disease, °/o
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`LATREILLE ET AL
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`26
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`74
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`84
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`status of 1, and received cisplatin 75 mg/m2 or greater for
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`lung or ovarian cancer.
`5
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`Arm A Versus Arm B
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`The outcomes listed above (TCE, CCE, VC, NC) as well
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`as mean nausea severity scores were compared in the two
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`groups over 7 days. No differences between the arms were
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`found in any of the analyses. Results for the 7-day period
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`according to these outcomes are listed in Table 2. Figure l
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`graphically displays the time to first emesis i11 each arm. It is
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`evident that antiemetic therapy failed in most patients within
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`the first 24 hours, but some patients developed their first
`episode of emesis after this time. Because the Italian Group
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`for Antiemetic Research“ suggested that continuation of
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`5—HT3 antagonists after 24 hours was only beneficiallin
`patients who had vomited before that time, we looked for a
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`similar effect in this trial. However, we found no significant
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`difference between the two maintenance arms whether or not
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`patients had vomited in the acute phase.
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`Although patients experienced marked changes in several
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`quality-of-life measures from baseline to day 8, differences
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`between the arms in this regard were slight. There were no
`significant differences in the functional domains or in global
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`Outcome
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`Table 2. Outcomes Arm A Versus Arm B
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`Arm A
`Arm B
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`(n = 219)
`(n = 216)
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`22
`25
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`36
`33
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`37
`36
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`23
`27
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`TCE, %
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`CCE, %
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`VC, %
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`NC, %
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`Mean nausea severity on
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`VAS
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`‘For the difference in proportions.
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`l 0.5 m
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`10.5 mm
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`P
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`.59
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`.54
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`.85
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`.33
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`.
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`95% Cl‘
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`-1 1-6
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`-6-] 3
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`-8-] l
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`—l3-4
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`—2—2
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`PTX-218.0005
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`Page 5 of 7
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`

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`DELAYED EMESIS AFTER HIGH-DOSE CISPLATIN
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`1177
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`apy. To our knowledge, no trial has addressed the benefit of
`adding one of the drugs to an agent with known activity in
`patients who receive highly emetogenic chemotherapy. The
`study most similar to this study was reported recently by the
`Italian Group for Antiemetic Research, which compared
`dexamethasone plus ondansetron to dexamcthasone plus
`metoclopramide in this setting. Although there was no
`overall difference, a subgroup analysis indicated that the
`ondansetron-containing arm might be preferred in patients
`who suffer from acute vomiting.‘ A similar analysis of our
`data shows no such tendency,.ie,
`the impact of adding
`granisetron was equivalent in patients who did or did not
`vomit
`in the first 24 hours. Furthermore,
`in a recently
`reported study that compared dolansetron and dexametha-
`sonc to dexamethasonc and ondansetron in moderately
`emetogenic chemotherapy,9 we also failed to find a differen-
`tial benefit to adding a 5-HT3 antagonist in patients who
`vomited in the first 24 hours. Therefore, we have no basis to
`recommend the continuation of these drugs to control
`delayed emesis in any subset of patients who receive highly
`emetogenic chemotherapy.
`What is not clear from these and other results is the
`
`optimal regimen for control of delayed emesis in patients
`who receive cisplatin, The results of the trial of Italian Group
`for Antiemetic Research indicate that the combination of a
`
`5-HT; antagonist and dcxamethasone is at least as effective
`as metoclopramide and dexamethasone. Taking these find-
`ings together with our results that show no benefit to the
`addition of a 5-HT3 antagonist to dexamethasone, one could
`conclude that dexamethasone alone is as effective as any
`other regimen in the control of delayed emesis. However, the
`trial of Kris et al2 suggested that metoclopramide and
`dexamethasone were superior to dexamethasone alone. It
`seems unlikely that the effect of granisetron differs from that
`of ondansetron in this setting because large randomized
`trials have shown the drugs to be equivalent.‘>1° Adding
`metoclopramide or a 5—HT3 antagonist to dexamethasoue
`may confer a modest increase in control of emesis. However,
`in light of our study results, this perceived benefit may not be
`great enough, nor the evidence strong enough, to support
`routine use of 5-HT3 antagonists for all patients in this
`setting.
`
`1'lme (hours)
`
`Fig I. Vomiting control arms Aversus arm 3. Am A (—); arm 8 (--).
`
`quality of life. Patients on arm B did, however, develop more
`sleeplessness (9 points greater on a 100-point scale; P = .0l),
`whereasthose on am A became more constipated (8 points
`greater; P = .04) and had an increased lack of appetite (8
`points greater: P = .03).
`
`DISCUSSION
`
`This study showed that the addition of granisetron to
`dexamethasone on days 2 through 7 after the administration
`of cisplatin in doses greater than 50 mg/m2 had no discern-
`able effect on the control of delayed nausea and vomiting.
`Although both 5-1-IT3 antagonists and steroids have in sonre
`trials been shown to be more active than placebo in this
`setting, the combination did not result in an additive effect in
`controlling delayed symptoms in this study. Therefore, even
`with the best available therapy, a substantial proportion of
`patients will not experience control of their delayed emesis
`after cisplatin. Although this proportion may vary depending
`on the dose of cisplatin, the definition of failure, and how
`missing data are treated, it was greater than 50% by any
`measure used in this study even in patients who received
`between 50 and 75 mg/m2 of cisplatin, which indicates that
`the population studied was at substantial risk for this
`problem.
`Few studies have assessed the role of 5-HT; antagonists in
`the control of delayed nausea and vomiting after Chemother-
`
`APPENDIX
`
`Collaborators: Robert N. Grimshaw, Robert C. Fraser, Sharon Hebh, Nova Scotia Cancer Tieatment and Research Foundation, Halifax; Francis
`Laberge, Carolle St Pierre, Hépital Laval, Quebec; Jean Latreille, Jean Saint-Louis, Anrlrée Marceau, Htitel-Dieu de Montreal, Monueal; Louise
`Yelle,,Kar] Bélanger, Lise Gagné, Hfipital Notre-Dame, Montreal; Adrian Langleberr. Arlene Lund, McGill University, Montreal; Raymond Guévin,
`MaIie—Paule Deschamps, l-lépital Saint Luc. Montréal; Peter Bryson, John Jeffrey, Bernadine Cowpcrthwaite, Kingston Regional Cancer Centre,
`Kingston; Dnvid Stewart, Diane Lister, Ottawa Regional Cancer Centre, Ottawa; Brian Findlay, Janice Gicsbrecht, Elaine Ravelle, Hotel Dierr
`Hospital, St Catharines; James Rusthoven, Hal Hirte, Nancy Ross, Hamilton Regional Cancer Centre, Hamilton; Winston Chow, Brita Promane, York
`
`Page 6 of 7
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