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Comment—Is There a Role for Low Doses of Mitotane (o,p'-DDD) as Adjuvant Therapy in Adrenocortical Carcinoma?

Otello Daniele, and Marco Boscaro University of Padova City Hospital of Padova Padova 35128, Italy

The paper by Dickstein et al. (1) describes four patients with localized adrenocortical carcinoma who received low-dose (1.5–2.0 g/day) adjuvant mitotane therapy postoperatively and continued the drug during follow-up. Of these patients, two remained disease-free 57 and 21 months after surgery, one died of an unrelated reason 68 months after surgery, and one developed lung metastases 48 months after surgery. Notwithstanding the limited number of patients examined, the authors conclude that low doses of mitotane might improve disease-free survival in adrenocortical carcinoma.

The role of mitotane as adjuvant treatment for adrenocortical carcinoma is controversial (1, 2, 3, 4, 5, 6, 7, 8). Our experience with adjuvant mitotane (8), as that of others (3, 4, 5, 6), indicates that it is not beneficial in terms of either disease freedom or survival.

We expanded our observation, and, of 59 consecutive patients (36 females, 23 males) with adrenocortical carcinoma (34 functioning and 25 nonfunctioning), 26 (44%) with localized or regional disease (median tumor size, 8.0 cm; range, 4.6–25.0 cm) underwent complete resection of the tumoral mass. Of these, 11 patients (group 1: 7 females and 4 males) received mitotane (o,p'-DDD, Lysodren, Bristol-Myers Squibb) postoperatively at doses of 4–8 g daily, whereas 15 patients (group 2: 9 females and 6 males) were given no medical treatment. The two groups were similar with regard to sex, age, tumor size, functional status, and tumor staging at diagnosis. Six patients of group 1 were free of disease at last follow-up (range: 6–82 months after surgery), and 5 developed metastases or recurrences (disease free-intervals of 4–29 months); 3 of them died of the disease 24–40 months after diagnosis. Of group 2, 6 were free of disease at last follow-up (range, 14–74 months after surgery), and 9 developed metastases (disease free-intervals of 8–60 months), 8 of them died during follow-up (survival: 15–104 months). Cumulative disease-free interval and survival rates, estimated with the Kaplan-Meyer method and compared with the log-rank test, were not significantly different between the two groups (² = 0.26, df = 1, P NS; and ² = 1.15, df = 1, P NS, respectively; Fig. 1). Owing to these disappointing results and the side-effects of mitotane, which significantly worsen quality of life of patients, we would not advocate mitotane as adjuvant treatment of adrenocortical carcinoma. However, prospective studies are needed to evaluate the real efficacy of this compound.

View larger version (17K): [in this window] [in a new window]   Figure 1. Effect of adjuvant mitotane (n = 11) compared with no treatment (n = 15) on the disease-free interval in patients with localized or regional adrenocortical carcinoma.

Footnotes

Address correspondence to: Luisa Barzon, Division of Endocrinology, Institute of Semeiotica Medica, Via Ospedale 105, Padova 35128, Italy.

Received January 7, 1999.

References

1. Dickstein G, Shechner C, Arad E, Best L-A, Nativ O. 1998 Is there a role for low doses of mitotane (o,p'-DDD) as adjuvant therapy in adrenocortical carcinoma? J Clin Endocrinol Metab. 83:3100–3103.[Abstract/Free Full Text]
2. Schteingart DE, Motazedi A, Noonan RA, Thompson NW. 1982 Treatment of adrenal carcinoma. Arch Surg. 117:1142–1146.[Abstract]
3. Bodie B, Novick AC, Pontes JE, et al. 1989 The Cleveland Clinic experience with adrenal cortical carcinoma. J Urol. 141:257–260.[Medline]
4. Luton JP, Cedars S, Billaud L, et al. 1990 Clinical features of adrenocortical carcinoma, prognostic factors and the effect of mitotane therapy. N Engl J Med. 322:1195–1201.[Abstract]
5. Vassilopoulou-Sellin R, Guinee VF, Klein MJ, et al. 1993 Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer. Cancer. 71:3119–3123.[CrossRef][Medline]
6. Haak HR, Hermans J, van de Velde CJR, et al. 1994 Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients. Br J Cancer. 69:947–951.[Medline]
7. Kasperlik-Zaluska AA, Migdalska BM, Zgliczynski S, Makowska AM. 1995 Adrenocortical carcinoma. A clinical study and treatment results of 52 patients. Cancer. 75:2587–2591.[CrossRef][Medline]
8. Barzon L, Fallo F, Sonino N, Daniele O, Boscaro M. 1997 Adrenocortical carcinoma: Experience in 45 patients. Oncology. 54:490–496.[Medline]

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