Frequent disease progression and early recurrence in patients with familial ovarian cancer primarily treated with paclitaxel and cis- or carboplatin (preliminary report)

Purpose: To evaluate frequencies of early disease progressions and recurrences in patients with familial vs sporadic ovarian cancers following primary paclitaxel/cis- or carboplatin chemotherapy.

Methods: The frequencies of disease progression up to six months following primary paclitaxel/cis- or carboplatin and of early disease recurrences were analysed in 18 Stage III patients with familial ovarian cancers, both carriers and non-carriers of 5382 insC BRCA1 mutation, and in 35 patients with Stage III sporadic ovarian tumors.

Results: Progressive disease within first six months following chemotherapy developed in 5/18 patients with familial cancers vs. 5/35 patients with sporadic tumors. Early disease recurrences (up to 6 months after treatment) occurred in 3/18 patients with familial vs. 2/35 patients with sporadic tumors. Recurrences after 7-12 months following treatment occurred, respectively, in 3/13 and 3/31 patients from these groups.

Conclusion: The results of this preliminary report may suggest that patients with familial ovarian tumors respond less favourably to paclitaxel/cis- or carboplatin treatment than patients with sporadic ovarian tumors. These findings should be however confirmed in a prospective study on a larger group of patients.

Familial ovarian cancer; BRCAJ mutations; Primary treatment failures; Paclitaxel/platin

[1] Claus E. B., Schildkraut J. M., T hompson W. D. et al.: "The genetic attributable risk of breast and ovarian cancer". Cancer, 1996, 77, 2318.

[2] Lichtenstein P., Holm N. V., Verkasalo P. D. et al.: "Environmental and heritable factors in the causation of cancer. Analysis of cohorts of twins from Sweden, Denmark, and Finland". N Eng. J. Med., 2000, 343, 78.

[3] Rubin S. C., Benjamin I., Behbakht K. et al.: "Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA l". N Engl. J. Med., 1996, 335, 1413.

[4] Aida H., Takakuwa K., Nagata H. et al.: "Clinical features of ovarian cancer in Japanise women with germ-line mutations of BRCA l". Clin. Cancer Res., 1998, 4, 235.

[5] Pharoah P. D. P., Easton D. F, Stockton D. L. et al.: "Survival Ill familial, BRCA 1- associated, and BRCA 2- associated epithelial ovarian cancer". Cancer Res., 1999, 59, 868.

[6] Boyd J., Sonoda Y., Federici M. G. et al.: "Clinicopathologic features of BRCA - linked and sporadic ovarian cancer". J. Amer. Med. Assoc., 2000, 283, 2260.

[7] Ben David Y., Chetrit A., Hirsh-Yechezkel G. et al.: "Effect of BRCA mutations on the length of survival in epithelial ovarian tumors". J. Clin. Oneal., 2002, 20, 463.

[8] Buller R. E., Anderson B., Connor J. P., Robinson R.: "Familial ovarian cancer". Gynecol. Oneal., 1993, 4, 160.

[9] Cannistra S. A. : "BRCAJ mutations and survival in women with ovarian cancer" (letter). N Engl. J. Med., 1997, 336, 1254.

[10] Whitmore S. E.: "BRCAJ mutations and survival in women with ovarian cancer" (letter). N Engl. J. Med., 1997, 336, 1254.

[11] Modan B.: "BRCAJ mutations and survival in women with ovarian cancer" (letter). N Engl. J. Med., 1997, 336, 1255.

[12] Johannsson 0. T., Ranstam J., Borg A., Olsson H.: "BRCAJ mutations and survival in women with ovarian cancer" (letter). N Engl. J. Med., 1997, 336, 1255.

[13] Brunet J.-S., Narod S. A., Tonin P., Foulkes W. D.: "BRCAJ mutations and survival in women with ovarian cancer" (letter). N. Engl. J. Med., 1997, 336, 1256.

[14] Johannsson O. T., Ranstam J., Borg A. et al.: "Survival of BRCAI breast and ovarian cancer patients: a population-based study from southern Sweden". J. Clin. Oneal., 1998, 16, 397.

[15] Scully R. et al.: "Association of BRCAJ with Rad51 in mitotic and meiotic cells". Cell, 1997, 88, 265.

[16] Sharan S. K., Morimatsu M., Albrecht U. et al.: "Embryonic lethality and radiation hypersens巾vity mediated by Rad 51 in mice lacking Brea 2". Nature, 1997, 386, 804.

[17] Chabner B. A., Meyers C. E.: "Clinical pharmacology of cancer chemotherapy". In: "Cancer: Principles and Practice of Oncology". De Vita V.T. jr., Hellman S. and Rosenberg S.A. (eds.). Philadelphia, J. B. Lippincott, 1989, 349.

[18] Rowinsky E. K., Onetto N., Canetta R. et al.: "Taxol: The first of three taxans, an important new class of antitumor agents". Sem. Oneal., 1992, 19, 646.

[19] Calvert A. H., Newel D. R., Gumbrell L. A. et al.: "Carboplatm dosage: Prospective evaluation of a simple formula based on renal function". J. Clin. Oneal., 1989, 7, 1748.

[20] Davelaar E. M., Bonfrer J. M. G., Verstraeten R. A. et al.: "CAl25: A valid marker in ovarian carcionoma patients treated with paclitaxel?". Cancer, 1996, 78. 118.

[21] Gordon J. S., Rustin B., Marples M. et al.: "Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels". J. Clin. Oneal., 2001, 19, 4054.

[22] Sambrook F., Fritsch E. F., Maniatis T.: "Molecular Cloninig. A Laboratory Manual". Cold Spring Harbor, Cold Spring Harbor Laboratory, 1989. Book 2: "Isolation of high-molecular weight DNA from mammalian cells", 9.16.

[23] Paszko Z., Skasko E., Wireniewska A. et al.: "Changes in BRCAI gene in patients with familial breast cancer in the Warsaw region of Poland". Nowotwory J. Oneal., 2002, 52, 97.

[24] Friedman L. S., Ostermeyer E. A., Szabo C. I. et al.: "Confirmation of BRCAI by analysis of germline mutations linked to breast and ovarian cancer in ten families". Nature Genet., 1994, 8, 399.

[25] Couch F. J. and Hartmann L. C.: "BRCAJ testing: advances and retreats". J. Amer. Med. Assoc., 1998, 279, 955.

[26] Grzybowska E., Zientek H., Jasiriska A. et. al.: "High frequency of recurrent mutations in BRCAI and BRCA2 in Polish families with breast and ovarian cancer". Hum. Muta/., 2000, 16, 482.

[27] Gorski B., Byrski T., Hazurski T. et al.: "Founder mutations in the BRCAI gene in Polish families with breast-ovarian cancer". Am. J. Hum. Genet., 2000, 66, 1963.