Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.

Rustin, G. J. S.; Newlands, E. S.; Lutz, Jean Michel; Holden, L.; Bagshawe, K. D.; Hiscox, J. G.; Foskett, Marianne; Fuller, S. H.; Short, Dee

doi:10.1200/jco.1996.14.10.2769

Cited by 164 publications

(64 citation statements)

References 17 publications

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“…This is important as it has been shown that, whilst chemotherapy regimens are highly efficacious, even the least toxic regimens used can be associated with significant sideeffects (Gillespie et al, 1997;Sharma et al, 1999) and the more rigorous regimens can be associated with long-term sequelae (Rustin et al, 1987(Rustin et al, , 1996. A stringent treatment policy does mean that definitive chemotherapy will be delayed in some patients.…”

Section: Discussionmentioning

confidence: 99%

Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy

Gillespie

Kumar

Hancock³

2000

Br J Cancer

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Of 4257 patients with gestational trophoblastic disease (GTD) registered between 1986 and 1996 with the Trophoblastic Screening and Treatment Centre, Sheffield, 231 women required chemotherapy; 28 were treated 24 weeks or more after the initial evacuation of products of conception. In 18 patients late treatment was a result of a predetermined watch and wait policy on the part of the Centre; these patients formed the study group. Patients were identified from the Centre's computer database. The time interval from first evacuation (diagnosis) to start of chemotherapy was calculated for each patient. Hospital records were reviewed when the interval of observation was 24 weeks or greater to determine patient characteristics, treatment and outcome. Eighteen women were treated ‘late’ (according to Centre policy), with a median age of 30 years (range 21–57 years). The interval from diagnosis to treatment ranged from 24 to, in one case, 56 weeks (median 33 weeks). Fourteen of 18 women had complete moles, 3/18 had partial moles and one had unclassified disease. All women had low-risk disease and were treated with single-agent methotrexate; 17 were cured with this regimen, one also required salvage chemotherapy. In conclusion, where a successful surveillance programme is in operation for GTD, a wait and watch policy can be adopted without compromising patients whose definitive treatment is commenced more than 6 months after the initial diagnosis. © 2000 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 99%

Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy

Gillespie

Kumar

Hancock³

2000

Br J Cancer

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“…In contrast, EMA -CO causes alopecia and myelosuppression, brings forward the menopause by 3 years and increases the risk of second malignancies by approximately 1.5 fold (Rustin et al, 1996;Bower et al, 1998). As a result, many patients select MTX -FA treatment, whereas some choose EMA -CO in the belief that it is more likely to cure them rapidly.…”

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confidence: 98%

“…However, none of these studies have addressed the outcome for patients with an hCG 4100 000 IU l À1 who still score in the low-risk category. The EMA/CO regimen is associated with greater toxicity than low-risk single-agent treatment, including alopecia, myelosuppression, a reduction in the age of menopause and the increased risk of a second malignancy (Rustin et al, 1996;Bower et al, 1998). As low-risk MTX -FA conveys less toxicity, should patients with lowrisk FIGO scores but with high hCG values at least be offered this treatment initially?…”

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The management and outcome of women with post-hydatidiform mole ‘low-risk’ gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l−1

et al. 2010

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Background: Gestational trophoblastic neoplasia (GTN) after a hydatidiform mole is either treated with single- or multi-agent chemotherapy determined by a multifactorial scoring system. Women with human chorionic gonadotrophin (hCG) levels >100 000 IU l −1 can remain within the low-risk/single-agent category and usually choose one drug therapy. Here we compare the success and duration of single- vs multi-agent chemotherapy in this patient group. Methods: Between 1980 and 2008, 65 women had a pre-treatment hCG >100 000 IU l −1 and were low risk. The initial hCG level, treatment regimens, changes and duration and overall survival were recorded. Results: Of 37 patients starting low-risk/single-agent treatment, 11 (29.7%) were treated successfully, whereas 26 (70.3%) required additional multi-agent chemotherapy to achieve complete remission (CR). Combination chemotherapy was initially commenced in 28 women, and 2 (7%) required additional drugs for CR. The overall duration of therapy for those commencing and completing single- or multi-agent chemotherapy was 130 and 123 days ( P =0.78), respectively. The median-treatment duration for patients commencing single-agent but changing to multi-agent chemotherapy was 13 days more than those receiving high-risk treatment alone (136 vs 123 days; P =0.07). All 3 patients with an initial hCG >400 000 IU l −1 and treated with single-agent therapy developed drug resistance. Overall survival for all patients was 100%. Conclusion: Low-risk post-molar GTN patients with a pre-treatment hCG >100 000 and <400 000 IU l −1 can be offered low-risk single-agent therapy, as this will cure 30%, is relatively non-toxic and only prolongs treatment by 2 weeks if a change to combination agents is required. Patients whose hCG is >400 000 IU l −1 should receive multi-agent chemotherapy from the outset.

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“…Similarly, in our series only 3 patients experienced Grade 1 acne form rash and, whereas this toxicity is not well characterized in the literature due to a lack of prospective analysis, it is our impression that it occurred less frequently and less severely than in the 5-day regimen. Also, the use of etoposide (arguably the most effective single drug to treat GTN) confers an increased risk of acute myelocytic leukemia, colon cancer, and premature menopause, 18 important issues to consider in a young, highly curable patient population.…”

Section: Discussionmentioning

confidence: 99%

Phase II trial of pulse dactinomycin as salvage therapy for failed low‐risk gestational trophoblastic neoplasia

Covens

Filiaci

Burger

et al. 2006

Cancer

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BACKGROUND The purpose of the study was to determine the activity and toxicity of pulse dactinomycin as salvage treatment of patients with low‐risk gestational trophoblastic neoplasia (GTN) who failed methotrexate therapy. METHODS Eligible patients had persistent/recurrent low‐risk GTN defined by changes in serum human chorionic gonadotropin (hCG) levels (<10% fall over 3 consecutive weekly titers, >20% rise over the previous value, or a rise after attaining institutional normal [>5 mu/mL]); World Health Organization (WHO) score 2–6; Gynecologic Oncology Group (GOG) performance status 0–1; and previous treatment restricted to methotrexate. Dactinomycin administration was 1.25 mg/m2 intravenous (i.v.) every 2 weeks until documented complete response (CR) or treatment failure. CR was defined as an institutional normal serum hCG level sustained for ≥4 consecutive weeks; treatment failure was a <10% fall (3 assays over 4 weeks) or >20% rise (over previous value) in hCG serum level. Levels were monitored biweekly × 8 weeks beyond the first normal value, then monthly × 10. RESULTS Five of 44 enrolled patients were ineligible due to choriocarcinoma and normal pretreatment serum hCG level (2 each), no history of methotrexate (1), and 1 patient with documented phantom hCG syndrome was unevaluable. In all, 28 of 38 (74%) evaluable patients attained CR. The median number of cycles was 4 (range, 2–10). Severe toxicity was minimal, causing no patient to discontinue therapy. All treatment failures achieved a CR after receiving subsequent chemotherapy; 3 patients also underwent hysterectomy. CONCLUSION Pulse dactinomycin is an active regimen for patients withlow‐risk GTN who fail previous methotrexate therapy. Cancer 2006. © 2006 American Cancer Society.

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Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.

Abstract: This study suggests that there is a slight increased risk of second tumors after sequential or combination chemotherapy for GTT. This has become apparent since the introduction of etoposide and longer follow-up.

Cited by 164 publications

References 17 publications

Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy

Treatment of persistent trophoblastic disease later than 6 months after diagnosis of molar pregnancy

The management and outcome of women with post-hydatidiform mole ‘low-risk’ gestational trophoblastic neoplasia, but hCG levels in excess of 100 000 IU l−1

Phase II trial of pulse dactinomycin as salvage therapy for failed low‐risk gestational trophoblastic neoplasia

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