© 2004 by Oxford University Press
© 2004 Oxford University Press
CORRESPONDENCE |
Re: New Guidelines to Evaluate the Response to Treatment in Solid Tumors (Ovarian Cancer)
Affiliations of authors: Medical Research Council Clinical Trials Unit, London, U.K. (GR); The Australian and New Zealand Gynaecological Oncology Group, Victoria, Australia (MQ); The Gynecologic Oncology Group, Philadelphia, PA (TT); Arbeitsgemeinschaft Gynaekologische Onkologie (ADB); Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens, Paris, France (EPL); The Nordic Society of Gynecological Oncology, Linkóping, Sweden (AJ); National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada (EE); Japanese Gynecologic Oncology Group, Tokyo, Japan (SS); Radiation Therapy Oncology Group, Philadelphia (KG); The European Organisation for Research and Treatment of Cancer, Brussels, Belgium (IV); Spanish Group for Research on Ovarian Cancer, Barcelona, Spain (AC); Gynaecologic Cancer Intergroup, Bethesda, MD (JV)
Correspondence to: Gordon J. S. Rustin, MD, FRCP, Mount Vernon Hospital, Department of Medical Oncology, The Clock Tower, Northwood, Middlesex, HA6 2RN, U.K. (e-mail: gordon.rustin{at}whht.nhs.uk)
The Gynaecologic Cancer Intergroup (GCIG) believes that definitions for response and progression of ovarian cancer according to serum CA 125 levels should be incorporated into ovarian cancer clinical trial protocols for relapse therapy. Although the GCIG is convinced of the value of the definition of progression that incorporates both Response Evaluation Criteria in Solid Tumors (RECIST) and CA 125 criteria and which should be used to define date of progression (1,2), the response definition as defined by Rustin (3) could benefit from further simplification. On the basis of the available data and extensive discussions among the cooperative groups within the GCIG, we recommend that the following definition of response be used in ovarian cancer trials so that response can be measured by either RECIST or CA 125 criteria. If the response is evaluable by both criteria, then the date of response will be the date of the earlier of the two events.
A response according to CA 125 has occurred if there is at least a 50% reduction in CA 125 levels from a pretreatment sample. The response must be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA 125 only if they have a pretreatment sample that is at least twice the upper limit of normal and within 2 weeks prior to starting treatment.
The date when the CA 125 level is first reduced by 50% is the date of the CA 125 response. To calculate CA 125 responses accurately, the following rules apply: 1) Intervening samples and the 28-day confirmatory sample must be less than or equal to (within an assay variability of 10%) the previous sample. 2) Variations within the normal range of CA 125 levels will not interfere with the response definition. We recommend that, in an ideal situation, CA 125 measurements be taken at specific time intervals. The first sample would be collected within 2 weeks before treatment is started, and later samples would be collected at intervals of 2–4 weeks during treatment and at intervals of every 2 or 3 months during follow-up. For each patient, the same assay method must be used and the assay must be tested in a quality-control scheme. Patients are not evaluable by CA 125 if they have received mouse antibodies or if there has been medical and/or surgical interference with their peritoneum or pleura during the previous 28 days.
This CA 125 response definition has been produced to evaluate relapse therapy. If assessing therapy that includes two treatment modalities for relapse (e.g., surgery and chemotherapy), any CA 125 response results from both treatments, and it should be clearly stated that CA 125 cannot distinguish between the effects of each treatment. To calculate response rates in protocols, an intent-to-treat analysis should be used that includes all patients with an initial CA 125 level of at least twice the upper limit of normal as eligible and evaluable. In addition to calculating response rates in protocols, it is advisable to record those patients who have both a CA 125 response and whose CA 125 level falls to within the normal range (4).
Gavin Shreeves supervised an independent validation of this definition by Justine Rochon for the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO; Munich, Germany), Desiré Paraiso for Group d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO; Paris, France), and Margot Osinski for The Australian and New Zealand Gynaecological Oncology Group. An example of its use can be seen on the Gynaecologic Cancer Intergroup Web site (http://ctep.info.nih.gov/resources/gcig/ index.html).
REFERENCES
1 Vergote I, Rustin GJ, Eisenhauer EA, Kristensen GB, Pujade-Lauraine E, Parmar MK, et al. Re: new guidelines to evaluate the response to treatment in solid tumors (ovarian cancer). J Natl Cancer Inst 2000; 92: 1534–5.
2 Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92: 205–16.
3 Rustin GJ. Use of CA-125 to assess response to new agents in ovarian cancer trials. J Clin Oncol 2003; 21(10 Suppl): 187–93.
4 Guastalla JP, Vincent P, Rol A. CA 125 evaluation of chemotherapy response in patients with recurrent ovarian cancer: Rustin criteria revisited [abstract]. Proc ASCO 2002; 21: 204a.
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J Natl Cancer Inst 2005 97: 151.
J Natl Cancer Inst 2005 97: 152.
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