Micha Jp

Interferon alpha-n1 (wellferon) for refractory genital warts: Efficacy and tolerance of low dose systemic therapy

This multi-center trial compared two doses of parenterally administered interferon alpha-n1 (Wellferon) in men and women with recurrent/resistant genital warts. Patients received either 1 or 3 MU/m2 daily for 14 days, then 3 times weekly for 4 weeks; non-responders could receive an additional four weeks of treatment. A total of 107 patients were enrolled, and 102 were evaluable after six weeks of study. The principal dose comparison was in 57 women assigned alternately to the two doses. Median lesion measurements were reduced significantly from baseline at weeks 2, 4 and 6 in both groups. Statistical analysis showed no difference in response to 1 versus 3 MU/m2. The overall complete response (CR) plus partial response (PR) rate at week 6 was 69% for the two doses. Two additional groups of 21 women and 24 men were treated at the higher dose with CR plus PR rates of 75 and 50%, respectively. Week 10 disease evaluations for all groups showed 19 of 77 patients to be completely cleared. Of these 19, only one had recurrent disease at the end of the 6-month study period. Analysis of the incidence of symptomatic side effects showed a significantly higher frequency among women treated with 3 MU/m2 than among women treated with 1 MU/m2. Five dose reductions and two withdrawals for toxicity occurred, all in the high dose group. This study demonstrates that parenterally administered Wellferon produces clearance of resistant genital warts in many patients, and that rates of clearance do not appear to vary between groups receiving moderate or low dose therapy.

Management of condyloma acuminatum

This article describes an approach to the evaluation and treatment of condyloma acuminatum (anogenital warts) that is based on the results of new clinical research on the biology of the human papillomavirus. A more extensive diagnostic protocol, including routine cervicovaginal examination and Papanicolaou smear, is proposed for female patients because of the close association of genital human papillomavirus infections with cervical carcinoma. Two highly effective therapies, cryosurgery and carbon dioxide laser photocoagulation, are described and compared with older regimens. Recent developments in immunotherapy for resistant condyloma acuminatum are also discussed.

A comparison of open surgery, robotic-assisted surgery and conventional laparoscopic surgery in the treatment of morbidly obese endometrial cancer patients.

Background and Objectives: The intent of this retrospective study was to assess the operative outcomes of morbidly obese endometrial cancer patients who were treated with either open surgery (OS) or a minimally invasive procedure. Methods: Morbidly obese (body mass index [BMI] > 40 kg/m2) patients with endometrial cancer who underwent OS, robotic-assisted laparoscopic surgery (RS), or conventional laparoscopic surgery (LS) were eligible. We sought to discern any outcome differences with regard to operative time, perioperative complications, and hospital stay. Results: Sixteen patients were treated with LS (BMI = 47.9 kg/m2), 13 were managed via RS (BMI = 51.2 kg/m2), and 24 underwent OS (BMI = 53.7 kg/m2). The OS (1.35 hours) patients had a significantly shorter operative duration than the LS (1.82 hours) and RS (2.78 hours) patients (P < .001); blood loss was greater in the OS (250 mL) group in comparison with the RS (100 mL) and LS (175 mL) patients (P = .002). Moreover, the OS (4 days) subjects had a significantly longer hospital stay than the LS (2 days) and RS (2 days) patients (P = .002). Conclusion: In the present study, we ascertained that minimally invasive surgery was associated with longer operative times but lower rates of blood loss and shorter hospital stay duration compared with treatment comprising an open procedure.

The subrenal capsule tumor implant assay as a predictor of clinical response to chemotherapy: 3 Years of experience

The clinical response to chemotherapy of a series of female patients with advanced pelvic malignancies was compared to the response of their tumors to the same agents in the murine subrenal capsule implant assay. A total of 194 different patients were studied in 242 different assays; 89.3% of the assays were evaluable. There were 83 prospective assays (assays performed before the patient received the chemotherapy) of 66 different patients for which clinical correlations were available. In these assays the sensitivity (frequency of positive test results in responding patients) was 85.0%, the specificity (frequency of negative test results in nonresponding patients) was 57.1%, and the efficiency (percentage correctly classified) was 63.9%. There were 100 retrospective assays (assays performed after the patient had been treated with the chemotherapy) of 69 different patients for which clinical correlations were available. In these assays the sensitivity was 66.7%, the specificity 70.7%, and the efficiency 70.0%. Thirty-one of the patients had both prospective and retrospective assays. There were 59 patients for whom the clinical response to chemotherapy could not be determined. It is believed that the clinical utility of the SRC assay has been validated by the good prospective sensitivity of the assay.

The safety and feasibility of robotic-assisted lymph node staging in early-stage ovarian cancer.

Objectives The purpose of this study was to report on the safety and feasibility of robotic-assisted systematic lymph node staging in the management of early-stage ovarian cancer. Methods We retrospectively reviewed the charts of presumed early-stage (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) ovarian cancer patients who underwent robotic-assisted surgery that incorporated a systematic pelvic and para-aortic lymphadenectomy from January 2009 until December 2013. Patient demographics, operative characteristics, pathology, lymph node counts, surgical complications, and hospital stay were evaluated. Results A total of 26 early-stage ovarian cancer patients were identified. The mean operating time was 2.90 hours, and the estimated blood loss was 63 mL; there were no intraoperative complications although 1 patient’s surgery was significantly prolonged due to pelvic adhesions. The mean number of pelvic and para-aortic lymph nodes removed was 14.6 (2.3% incidence of pelvic lymph node metastases) and 5.8 (3.3% incidence of para-aortic lymph node metastases), respectively. The patients’ mean duration of hospital stay was 18.4 hours, and 2 patients were readmitted for either a postoperative wound infection or vaginal dehiscence. Conclusions The results from this study suggest that robotic-assisted surgical staging in the management of presumed early-stage ovarian cancer is both feasible and associated with a minimal patient complication rate. We encountered a low incidence of lymph node metastases, and the readmission rate was favorable. Nevertheless, because the prevalence of lymph node metastases can approach 20% in select patients, physicians should consider a systematic lymph node resection to confer an optimal clinical assessment.

Malignant ovarian germ cell tumors: A review of thirty-six cases

Thirty-six patients with malignant ovarian germ cell tumors were treated between 1972 and 1983, including 16 with immature teratoma, five with endodermal sinus tumor, seven with dysgerminoma, and eight with mixed germ cell tumors. The median age at presentation was 18 years and mean primary tumor diameter was 18 cm. Twenty-five of the 27 patients who were treated with multiple-agent chemotherapy underwent second-look procedures, only two of which revealed persistent malignancy. No patients have developed recurrence after a negative second-look operation. Two of the three patients with failure of initial chemotherapeutic regimens had complete remissions with second regimens. Two patients have died of malignancy, one who presented with a Stage IA mixed germ cell tumor and one noncompliant patient with a Stage IA, grade 2 immature teratoma. The other 34 patients are alive without evidence of disease from 21 to 141 months, with a median follow-up of 68 months. These data confirm that multiple-agent chemotherapy has dramatically improved the prognosis for patients with malignant nondysgerminomatous ovarian germ cell tumors.

A pilot study evaluating a novel regimen comprised of carboplatin, paclitaxel, and bevacizumab for advanced-stage ovarian carcinoma.

Objectives: The purpose of this study was to assess the toxicity, progression-free survival, and response rate of advanced stage ovarian carcinoma patients treated with a novel regimen comprising paclitaxel, carboplatin, and bevacizumab. Methods: All eligible patients were treated with intravenous paclitaxel (80 mg/m2) on days 1, 8, and 15; carboplatin (area under the curve, 5) on day 1; and bevacizumab (10 mg/kg) on days 1 and 15; Q28 days for 6 cycles. Bevacizumab was administered during cycles 2 through 6. Results: Twenty patients received a combined total of 102 cycles of primary induction chemotherapy (median, 6; range, 2-6) and were evaluable for toxicity assessment. Six (5.9%) cycles were associated with grades 3 and 4 neutropenia, which resulted in the removal of 2 patients. Only 1 (0.98%) cycle was associated with grade 3 thrombocytopenia. Moreover, one patient developed a colorectal fistula and was subsequently removed from the study. Grade 3 hypertension was encountered and successfully managed in 3 participants. In the group of 13 patients who were evaluated for response, the overall response rate was 61.6% (30.8% complete response). Four patients exhibited stable disease, and 1 patient had progressive disease. The patient groups mean progression-free survival was 5.8 months. Conclusions: The tolerable hematologic toxicity and reasonable response rate after paclitaxel, carboplatin, and bevacizumab suggest that this regimen has moderate activity and can be safely administered to an advanced-stage ovarian carcinoma population. We were further encouraged by the reasonable incidence of hypertension. However, because 4 patients were removed from the study because of either grade ≥2 neutropenia or thrombocytopenia, we suggest that colony-stimulating factors and cautious patient observation should be considered with this regimen.

Clinical utility of CA-125 for maintenance therapy in the treatment of advanced stage ovarian carcinoma.

Abstract Maintenance therapy has been extensively studied to discern any prospective therapeutic advantage in the treatment of advanced stage ovarian carcinoma. The CA-125 assay may have prognostic benefit in determining whether this treatment regimen is appropriate for ovarian carcinoma patients who achieve a complete response to first-line therapy. We retrospectively documented the CA-125 levels of 2 advanced ovarian cancer patient groups who exhibited a clinically defined complete response to their primary induction therapy. Patients were then treated with a paclitaxel-based maintenance therapy regimen. The first group (group A; n = 13 patients) received 3 cycles of single-agent paclitaxel maintenance therapy, and the second group (group B; n = 13 patients) received 12 cycles of single-agent paclitaxel maintenance therapy. The premaintenance therapy CA-125 serum levels (<10 or ≥10 U/mL) of the 2 treatment groups were then retrospectively evaluated in an intragroup analysis to discern any relationship with progression-free survival (PFS) and overall survival. There was a statistically significantly relationship between the CA-125 levels (<10 U/mL) premaintenance therapy and PFS. The patients who had the lowest CA-125 levels exhibited the most favorable PFS results. Despite the limited sample size and nonrandomized nature of this study, these results are provocative and suggest that advanced ovarian cancer patients who achieve an excellent response to primary platinum-based chemotherapy with a CA-125 serum level less than 10 U/mL may be more amenable to the benefits of paclitaxel maintenance therapy.

A phase II, multicenter trial of weekly topotecan in patients with recurrent platinum-sensitive epithelial cancers of the ovary and peritoneum.

The purpose of this study was to evaluate the response rate and toxicity of weekly topotecan in patients with recurrent platinum-sensitive epithelial cancers of the ovary and peritoneum. Thirty-nine platinum-sensitive recurrent ovarian cancer patients received topotecan (4 mg/m2) intravenously day 1, day 8, day 15, every 28 days. Colony-stimulating factors were excluded from the study. Clinical response was assessed by clinical, serologic, and radiographic measures at the conclusion of cycle four. Patients received 136 cycles of topotecan (median = 3; range 1–6) and were evaluated for response and toxicity. Median number of prior regimens was one. Grade 3/4 neutropenia developed in 3 (7.7%) patients. Grade 3 thrombocytopenia was seen in one (2.6%) patient, with no incidence of grade 4 thrombocytopenia. There was no evidence of grade 3 anemia, but one patient (2.6%) was associated with grade 4 anemia. There was no grade 3 or 4 neuropathy. We encountered 18 dose reductions following less than or equal to grade 2 myelosuppression, necessitating the removal of eight (20.5%) patients prior to cycle four. Twenty-one (53.8%) patients were removed from the study due to disease progression. Following the completion of cycle four, four (10.3%) patients demonstrated stable disease and four (10.3%) patients exhibited a partial response. There were no complete responses. Median disease-free survival was 12 weeks. Weekly topotecan (4 mg/m2) demonstrated modest activity and was moderately well tolerated. However, the significant number of dose reductions and high incidence of patients who demonstrated disease progression suggests additional modifications with this specific regimen are necessary.

Action of 2-β-d-ribofuranosylthiazole-4-carboxamide (tiazofurin) against untreated human ovarian cancers in the murine xenograft assay

The activity of 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) was determined in nine untreated human ovarian cancer specimens, using the murine subrenal capsule xenograft assay. Tumor cytotoxic effect was demonstrated in seven out of the nine tumors implanted. The drug was well tolerated by the test animals. Tiazofurin may prove to be an effective chemotherapeutic agent in the treatment of ovarian cancer.