GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS).

BACKGROUND: First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS: This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR patients (metastatic, axial-pelvic primaries or bone marrow micrometastasis) received 2 window cycles of G/D. Patients with an objective response (OR) to G/D received 12 monthly cycles of G/D after completion of mP6. The primary end point was the OR rate to the G/D window phase and the event-free survival (EFS) and overall survival (OS) for all patients. The study is registered at ClinicalTrials.gov (identifier: NCT00006734). RESULTS: Forty-three patients were enroled, median age 17 years (range, 3-40). After a median follow-up of 43.4 months, the 5-year OS rate is 55.0% (95% CI, 41-74%) with an EFS of 50.0% (95% CI, 36-68%). The 5-year OS and EFS rates for standard risk (SR) patients was 76.0% (95% CI, 57-100%) and 71.0% (CI, 54-94%); for HR 36.0% (CI, 20-65%) and 29.0% (CI, 15-56%). Twelve of 17 (70.6%) high-risk (HR) patients showed an OR (7 PR and 5 SD) to G/D window therapy. The 5-year OS rate for patients ⩽18 years of age was 74.0% (CI, 56-97%) and 31.0% for >18 years (95% CI, 15-66%), P<0.001. Grade 4 adverse events during mP6 occurred in 28/39 of patients (72%) and did not correlate with age. Multivariate survival analyses with <18 vs ⩾18 and risk groups significant differences, P<0.00001. Using a Cox model for OS, both age and risk group were statistically significant (P=0.0011 and P=0.0065, respectively). CONCLUSIONS: Age at diagnosis is an independent prognostic factor superior to the presence of metastases with 18 years as the strongest cut-off. The mP6 regimen provided survival curves that plateau at 3 years and G/D produced significant responses in HR-ES that is worth further exploring.

Endometrial histology in long-term users of the once-a-month injectable contraceptive Cyclofem.

This study evaluated endometrial histology in women using the once-a-month injectable contraceptive Cyclofem for one year or more. The study received IRB approval. Seventeen Cyclofem users accepted to be submitted to an endometrial biopsy. All the samples were collected with an endometrial suction curette (Z-Sampler, ZSI Gynecological Product, Chasworth, CA, USA) in an outpatient clinic, 27-33 days after the last injection. The material was fixed immediately in Bouin solution prior to wax embedding and screened as a routine histological examination by a senior pathologist. The pathologist did not know the bleeding status of each woman or the number of injections each woman had received before the biopsy. All women recorded bleeding and spotting for the last 60 days prior to the biopsy. The mean age of volunteers was 25.9 years (range 21-32) and the mean number of injections received was 24.8 (range 14-47). The results were: 4 out of 17 biopsies were found to be inadequate for diagnosis because they consisted of only blood and mucus. Two of these women were bleeding regularly and the other 2 had amenorrhea. Eight endometrial samples presented a proliferative pattern and, in this group, 3 women had amenorrhea and 5 were bleeding regularly. The other 5 biopsies were reported as secretory endometrium, and 4 of them showed pseudodecidual reaction compatible with the administration of progestin. All of these women were bleeding regularly. The results of the biopsies were not related to the number of injections received nor to the age of the women. In conclusion, long-term administration of the injectable contraceptive Cyclofem did not produce adverse alterations in the endometrium as hyperplasia.

Return of fertility after discontinuation of the once-a-month injectable contraceptive Cyclofem.

The objective of this study was to evaluate the return of fertility in women who used Cyclofem as a contraceptive method during the introductory studies conducted in Brazil, Chile, Colombia, and Peru. From these four cohorts, 101 women were eligible for the study. Thirty-one were not included in the study either because they refused to be interviewed, had initiated another contraceptive method the month after discontinuation, or were unable to be contacted. A total of 70 women were included in the study. Our results showed that the return to fertility rate after the discontinuation of Cyclofem was 1.4 per 100 women at the end of the first month and reached 82.9 at one year. More than 50% were pregnant at 6 months. Fifty-one (94.4%) pregnancies ended in a live birth, two were spontaneous first trimester abortions, and one was a hydatidiform mole. Return of fertility was not related to the woman's age at the time of discontinuation, her weight, or the number of Cyclofem injections. In conclusion, fertility is restored by 1 month following Cyclofem discontinuation. Users and potential users should be counseled regarding the rapid return of fertility after discontinuing this method of contraception.

PIP: Cyclofem, a monthly injectable contraceptive containing 5 mg estradiol cypionate and 25 mg medroxyprogesterone acetate, has been registered in several Latin American countries; however, the return to fertility after method discontinuation has not been investigated. To address this issue, 70 women were followed who had participated in introductory studies in Brazil, Chile, Colombia, and Peru during 1992-94 and who then discontinued injectable use to achieve pregnancy. The mean number of Cyclofem injections was 7.1 (range, 1-19). The fertility rate was 1.4 at the end of the first month after Cyclofem discontinuation, 52.9 after 6 months, and 82.9 at 12 months. 55 pregnancies (94.8%) ended in live-term births, with no congenital malformations; there were 2 spontaneous abortions in the first trimester. The number of months required to become pregnant was not significantly associated with maternal age, body weight, number of injections, or country site. The return to fertility for this method is comparable to that following discontinuation of copper IUDs, barrier methods, and oral contraceptives. Since information on return to fertility is essential to informed choice, these findings should be incorporated into educational and counseling materials for providers and potential acceptors of this new contraceptive method.

Oral clindamycin and ciprofloxacin versus intramuscular ceftriaxone and oral doxycycline in the treatment of mild-to-moderate pelvic inflammatory disease in outpatients.

This multicenter, prospective, double-blind study compared the safety and efficacy of clindamycin and ciprofloxacin versus ceftriaxone and doxycycline in the treatment of outpatients with mild to moderate pelvic inflammatory disease (PID) diagnosed by laparoscopy. Samples taken from the endocervix, endometrium, and abdominal cavity before treatment and from the endocervix after treatment were cultured for aerobes, anaerobes, Neisseria gonorrhoeae, and Chlamydia trachomatis. Of the 138 patients enrolled, 131 were evaluable for efficacy. The most prevalent bacteria were streptococci, staphylococci, and Escherichia coli (among aerobes) and Bacteroides species and peptostreptococci (among anaerobes). N. gonorrhoeae was present in 2% (3) of the 131 evaluable patients, and C. trachomatis was in 11% (15). The clinical cure rate was 97% (65 of 67) in the clindamycin and ciprofloxacin group and 95% (61 of 64) in the ceftriaxone and doxycycline group. Side effects were similar in both groups. In conclusion, the two regimens for the outpatient treatment of mild to moderate PID were similarly effective and safe.