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Problems With Nomenclature and Pharmacodynamics in Trophoblastic Disease

Department of Obstetrics and Gynecology, School of Medicine, Yale University, New Haven, CT

To the Editor:

The article titled "Low Risk Persistent Gestational Trophoblastic Disease: Outcome After Initial Treatment With Low Dose Methotrexate and Folinic Acid from 1992 to 2000" by McNeish et al [1] deserves comment for at least two reasons. The first concerns the matter of clarification of trophoblastic neoplasia, and the second concerns the pharmacodynamics of chemotherapy used for these patients.

It is deservedly recognized by the trophoblastic community that it was Professor Kenneth Bagshawe at Charing Cross who initiated the idea of risk factor scoring in trophoblastic neoplasia. This scoring system was first adopted by the WHO and now in 2003 by the International Federation of Gynecology and Obstetrics (FIGO). It is the new FIGO 2000 classification that should now be the standard means of assessing risk factors and staging trophoblastic neoplasia.

The reporting of results of treatment of trophoblastic neoplasia has been bedeviled by the numerous idiosyncratic classifications and changes in scoring and staging that have been applied by various investigators throughout the world. In this article, the authors from the Charing Cross group failed to abide by the rules that they, themselves, helped create; they actively participated in the decision-making.

The second issue is a matter of so-called "drug resistance." Throughout this article, there is description of drug resistance when, in fact, the primary medications used were methotrexate with leucovorin rescue. All data from the use of this combination demonstrate a primary failure rate of 30% to 40%, with satisfactory rescue by other agents. What the authors fail to state is that if methotrexate had been used in a 5-day course without the leucovorin, it is likely that some 60% to 70% of these primary failures would have been converted to cures of the trophoblastic neoplasia, rather than requiring another single agent or even multiagent chemotherapy. It is the Charing Cross group that first drew attention to the incidence of leukemia following combination chemotherapy with etoposide, so it is agreed among the trophoblastic community that multiagent chemotherapy is preferably avoided if single-agent chemotherapy will do the job. The best way to achieve that goal is to use the same single agent in a 5-day course, and that procedure has 60% to 70% effectiveness. The alternate day methotrexate/leucovorin protocol has as high a failure rate as pulsed therapy with either methotrexate or actinomycin. All these drugs are cycle specific, and it is time that the trophoblastic community accepted that there is a chance the primary therapy may not be effective.

The Society of Gynecologic Oncologists has advocated that the conflict in whether clinical trophoblastic disease requiring chemotherapy on the basis of human chorionic gonadotropin persistence is pathologically benign or malignant is best avoided by use of the term "trophoblastic neoplasia." The authors do not abide by this rule either. It is a pity that one of the leading institutions treating trophoblastic neoplasia will not abide by the very rules it helped create.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCE

1. McNeish IA, Strickland S, Holden L, et al: Low-risk persistent gestational trophoblastic disease: Outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000. J Clin Oncol 20:1838-1844, 2002[Abstract/Free Full Text]

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• In Reply:
  Edward S. Newlands
  JCO 2004 22: 204 [Full Text]

Related Article

• Low-Risk Persistent Gestational Trophoblastic Disease: Outcome After Initial Treatment With Low-Dose Methotrexate and Folinic Acid From 1992 to 2000
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  JCO 2002 20: 1838-1844 [Abstract] [Full Text]

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