Background: Termination of pregnancy in the second trimester using prostaglandins has been shown to be safe and effective. Misoprostol has multiple routes of administration; oral, vaginal, buccal, rectal and sublingual Objective: The study aims to compare the efficacy and safety of intrauterine extra-amniotic and vaginal misoprostol in a dose of 200 microgram every 4 hours for the termination of pregnancy in cases of second trimester miscarriage. Materials and Methods: A Prospective randomized open labeled clinical trial included patients with missed miscarriage in gestational age between 13 and 24 weeks. Patients were randomized to receive subsequent doses of 200 µg misoprostol every 4 hours either intra uterine extra-amniotic by Foley catheter or vaginally administered. Randomization was completed using a computer-generated random table. The primary outcome of this study was the mean duration from the initial misoprostol dose until complete fetal expulsion (induction-expulsion interval). Results: The study included 180 women. The mean gestational age was 17.74 weeks. The mean time to complete miscarriage in the intra uterine extra-amniotic group was 5.27 hrs, which was significantly lower (p=0.001) than the vaginal group (9.92 hrs). Side effects were more common in the vaginal group. Conclusions: Intra uterine extra-amniotic misoprostol with a dose of 200 ug every 4 hours appears to be more effective and safer than vaginal misoprostol in induction of second trimester miscarriage. Registration number: (Clinical Trials. Gov; NCT02669420)

Aim: High-grade glioblastoma multiforme (GBM) has a poor median overall survival (OS). The standard treatment after surgery is temozolomide and radiotherapy (RTH). Patients with unmethylated methylguanine-methyltransferase promoter (MGMT) have no or little benefit from temozolomide and are eligible for alternative therapies. Gemcitabine is a good radiosensitizer. We aimed to evaluate the combination of gemcitabine with RTH in newly diagnosed GBM. Methods: The study was a prospective phase II study. Eligible patients were required to have histologically proven anaplastic astrocytoma or GBM. Patients underwent biopsies or subtotal resection. The treatment consisted of fixed-dose rate gemcitabine 175 mg/m2 weekly followed after 24 h by standard cranial RTH for 6 weeks. Tumor response was evaluated by Macdonald criteria. In case of progression, patients received temozolomide (200 mg/m2/5 days every 28 days). Results: Thirty patients with a median age of 52 years (30-69), 73%/27% male/female, the Eastern Cooperative Oncology Group performance status 1 (range 0-2) were enrolled. Five patients had a partial-response (17%) and 13 stable-disease (43%). Median time to progression was 7.88 months (95% CI 6.1-9.69) and OS was 11.77 months (95% CI 9.97-13.56). The treatment was well tolerated with grade-3 neutropenia in 3, grade-3 anemia in 2 and impaired liver enzymes in 1 patient. Conclusion: Gemcitabine followed by radiotherapy is active and promising regimen in newly diagnosed GBM. Gemcitabine uptake is easy, with a long local retention of active metabolites, precluding systemic side effects of radiosensitization. In a phase III study this treatment should be evaluated in patients with unmethylated MGMT promoter who will not benefit from temozolomide.

Aim: High-grade glioblastoma multiforme (GBM) has a poor median overall survival (OS). The standard treatment after surgery is temozolomide and radiotherapy (RTH). Patients with unmethylated methylguanine-methyltransferase promoter (MGMT) have no or little benefit from temozolomide and are eligible for alternative therapies. Gemcitabine is a good radiosensitizer. We aimed to evaluate the combination of gemcitabine with RTH in newly diagnosed GBM. Methods: The study was a prospective phase II study. Eligible patients were required to have histologically proven anaplastic astrocytoma or GBM. Patients underwent biopsies or subtotal resection. The treatment consisted of fixed-dose rate gemcitabine 175 mg/m2 weekly followed after 24 h by standard cranial RTH for 6 weeks. Tumor response was evaluated by Macdonald criteria. In case of progression, patients received temozolomide (200 mg/m2/5 days every 28 days). Results: Thirty patients with a median age of 52 years (30-69), 73%/27% male/female, the Eastern Cooperative Oncology Group performance status 1 (range 0-2) were enrolled. Five patients had a partial-response (17%) and 13 stable-disease (43%). Median time to progression was 7.88 months (95% CI 6.1-9.69) and OS was 11.77 months (95% CI 9.97-13.56). The treatment was well tolerated with grade-3 neutropenia in 3, grade-3 anemia in 2 and impaired liver enzymes in 1 patient. Conclusion: Gemcitabine followed by radiotherapy is active and promising regimen in newly diagnosed GBM. Gemcitabine uptake is easy, with a long local retention of active metabolites, precluding systemic side effects of radiosensitization. In a phase III study this treatment should be evaluated in patients with unmethylated MGMT promoter who will not benefit from temozolomide.

Aim: High-grade glioblastoma multiforme (GBM) has a poor median overall survival (OS). The standard treatment after surgery is temozolomide and radiotherapy (RTH). Patients with unmethylated methylguanine-methyltransferase promoter (MGMT) have no or little benefit from temozolomide and are eligible for alternative therapies. Gemcitabine is a good radiosensitizer. We aimed to evaluate the combination of gemcitabine with RTH in newly diagnosed GBM. Methods: The study was a prospective phase II study. Eligible patients were required to have histologically proven anaplastic astrocytoma or GBM. Patients underwent biopsies or subtotal resection. The treatment consisted of fixed-dose rate gemcitabine 175 mg/m2 weekly followed after 24 h by standard cranial RTH for 6 weeks. Tumor response was evaluated by Macdonald criteria. In case of progression, patients received temozolomide (200 mg/m2/5 days every 28 days). Results: Thirty patients with a median age of 52 years (30-69), 73%/27% male/female, the Eastern Cooperative Oncology Group performance status 1 (range 0-2) were enrolled. Five patients had a partial-response (17%) and 13 stable-disease (43%). Median time to progression was 7.88 months (95% CI 6.1-9.69) and OS was 11.77 months (95% CI 9.97-13.56). The treatment was well tolerated with grade-3 neutropenia in 3, grade-3 anemia in 2 and impaired liver enzymes in 1 patient. Conclusion: Gemcitabine followed by radiotherapy is active and promising regimen in newly diagnosed GBM. Gemcitabine uptake is easy, with a long local retention of active metabolites, precluding systemic side effects of radiosensitization. In a phase III study this treatment should be evaluated in patients with unmethylated MGMT promoter who will not benefit from temozolomide.

Aim: High-grade glioblastoma multiforme (GBM) has a poor median overall survival (OS). The standard treatment after surgery is temozolomide and radiotherapy (RTH). Patients with unmethylated methylguanine-methyltransferase promoter (MGMT) have no or little benefit from temozolomide and are eligible for alternative therapies. Gemcitabine is a good radiosensitizer. We aimed to evaluate the combination of gemcitabine with RTH in newly diagnosed GBM. Methods: The study was a prospective phase II study. Eligible patients were required to have histologically proven anaplastic astrocytoma or GBM. Patients underwent biopsies or subtotal resection. The treatment consisted of fixed-dose rate gemcitabine 175 mg/m2 weekly followed after 24 h by standard cranial RTH for 6 weeks. Tumor response was evaluated by Macdonald criteria. In case of progression, patients received temozolomide (200 mg/m2/5 days every 28 days). Results: Thirty patients with a median age of 52 years (30-69), 73%/27% male/female, the Eastern Cooperative Oncology Group performance status 1 (range 0-2) were enrolled. Five patients had a partial-response (17%) and 13 stable-disease (43%). Median time to progression was 7.88 months (95% CI 6.1-9.69) and OS was 11.77 months (95% CI 9.97-13.56). The treatment was well tolerated with grade-3 neutropenia in 3, grade-3 anemia in 2 and impaired liver enzymes in 1 patient. Conclusion: Gemcitabine followed by radiotherapy is active and promising regimen in newly diagnosed GBM. Gemcitabine uptake is easy, with a long local retention of active metabolites, precluding systemic side effects of radiosensitization. In a phase III study this treatment should be evaluated in patients with unmethylated MGMT promoter who will not benefit from temozolomide.

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