Pathologic response and toxicity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine in cervical cancer: a randomized Phase II study

PURPOSE: To compare gemcitabine and cisplatin (GC) with cisplatin (C) concurrent with radiotherapy in International Federation of Gynecology and Obstetrics Stage IB2, IIA, and IIB cervical carcinoma in a preoperative setting. The main endpoints were the pathologic response rate and toxicity. METHODS AND MATERIALS: A total of 83 patients were randomized to either C or GC. Treatment consisted of six doses of cisplatin at 40 mg/m(2) every week for Arm 1 (C) and six doses of gemcitabine at 125 mg/m(2) plus cisplatin at 40 mg/m(2) every week for or Arm 2 (GC) Both regimens were administered concurrent with 50 Gy of external beam radiotherapy in 2-Gy fractions for 5 weeks. After chemoradiotherapy, patients underwent radical hysterectomy. RESULTS: All 83 patients were studied for toxicity and 80 for response. The complete pathologic response rate in the C arm and GC arm was 55% (95% confidence interval, 35.5-73%) and 77.5% (95% confidence interval, 57-90%; p = 0.0201). Among those with a partial response, 7 patients each had high and intermediate-high risk factors for recurrence in their surgical specimens in the C arm vs. 2 and 3 patients, respectively, with these characteristics in the CG arm. The number of weekly doses and the dose intensity of GC were lower than for C. The time to complete external beam radiotherapy also favored the C arm. The CG combination produced greater GI and hematologic toxicity. CONCLUSION: The radiosensitizing combination of GC achieved a greater pathologic response rate than C in the treatment of cervical cancer.     

Induction chemotherapy with gemcitabine and oxaliplatin for locally advanced cervical carcinoma

Induction chemotherapy followed by surgery, particularly with newer agents or combinations, remains to be explored in locally advanced cervical cancer. Gemcitabine cisplatin is a very active combination for this tumor, therefore we explored the activity of gemcitabine in combination with oxaliplatin. Ten untreated patients with histologic diagnosis of cervical carcinoma and staged as IB2 to IIIB were treated with 3 21-day courses of oxaliplatin 130 mg/m day 1 and gemcitabine 1,250 mg/m days 1 and 8 followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated at the end of chemotherapy. All patients were evaluable. The overall clinical response rate was 80%, being complete in 3 patients (30%) and partial in 5 (50%). Seven (70%) patients underwent surgery, and three (30%) had chemoradiation as definitive treatment. Hematologic toxicity was moderate, with leukopenia grades III-IV in 17 and 0%; granulocytopenia grades III-IV in 23 and 3%, respectively. Eight patients had grade I oropharyngeal toxicity. At a median follow-up of 11 months (range: 10-12), all patients are disease free. Gemcitabine oxaliplatin is a very active and well-tolerated combination for locally advanced cervical cancer.     

Changing risk factors for HIV infection

BACKGROUND: HIV infection in women is a growing problem in developing countries. Risk factors for HIV infection vary from country to country and may change with time. METHODS: We describe a retrospective review of the epidemiologic characteristics and associated gynecologic diseases of all HIV-infected women seen at two tertiary-care hospitals in Mexico City. RESULTS: One hundred thirty consecutive patients were included in the study from March 1985 to January 1996. Mean age at HIV diagnosis was 36.2 years (range: 16-76). Of the 75 women diagnosed with AIDS prior to 1992, 58 (69%) were infected through blood transfusion and 17 (20%) through sexual contact. After January 1992, 11 (23%) acquired infection through blood transfusion and 28 (60%) through sexual contact; these differences were statistically significant (p <0.0001). Prior to 1992, 66 (90%) women presented in stage IV, whereas after that year only 29 (51%) (p <0.001) presented in stage IV. Of 92 patients on whom a cervico-vaginal smear was carried out, human papillomavirus infection was identified in 22 (24%) women, nine (9.8%) had morphologic evidence of a cervical intraepithelial neoplasia (four with mild or moderate dysplasia and five with in situ cervical carcinoma). Four patients had invasive cervical carcinoma. CONCLUSIONS: The main risk factor for HIV infection in Mexican women with AIDS changed from transfusion acquired to sexually acquired in 1992. As a country, we were successful in providing safe blood but failed to prevent sexual transmission. Our patients had a high frequency of cervical carcinoma and precursor lesions associated with human papilloma virus.     

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis to mountain cedar.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms. RESULTS: Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.     

Multimodal treatment of locally advanced cervical cancer

BACKGROUND: Radiation therapy with concomitant chemotherapy is the standard treatment for locally advanced cervical cancer. In Mexico, most patients are still treated with radiation therapy alone. The aim of this work was to demonstrate that results obtained with combined treatments in the Mexican population are similar to those reported in the literature. METHODS: Survival was analyzed in three sequential phase II studies of combined treatment: neoadjuvant chemotherapy followed by surgery (NEOCT+Sx) -February to July 1999; concomitant chemoradiotherapy (CT/RT) -August to December 1999; and neoadjuvant chemotherapy followed by surgery plus adjuvant chemoradiotherapy (NEOCT+Sx+CT/RT) -December 2000 to June 2001. These results were compared with a historical control group treated with radiation therapy alone between September and December 1998. The Kaplan-Meier product-limit method, log-rank test and Cox proportional hazards model were used for analysis. RESULTS: Results showed that the three combined modalities significantly reduced the risk of death. Treatment with NEOCT+Sx reduced the risk to 0.452 (95% CI 0.246-0.830), p=0.010. The risk reduction with CT/RT was 0.408 (95% CI 0.218-0.762), p=0.005, and for the group of patients receiving NEOCT+Sx+CT/RT risk was reduced to 0.365 (95% CI 0.169-0.787), p=0.010. The corresponding absolute survival benefit was 14% for patients in stages IB2-IIA, 24% for IIB, and 21% for stage IIIB. CONCLUSIONS: Within the limitations of a non-randomized study, our results are in agreement with those obtained from published randomized phase III trials which state that radiation therapy alone is a suboptimal treatment for locally advanced cervical cancer; hence, patients should receive cisplatin-based chemoradiotherapy as a standard treatment.     

Role of infectious diseases in human carcinogenesis

The burden of human infectious diseases remains a public health problem worldwide. At least 2 billion people are affected by viral infections, and a similar number by bacteria or helminths. The long-term effects of these maladies have raised particular concern since some infectious agents have been associated with chronic human diseases, especially cancer. It is estimated that 13-20% of the world cancer cases are associated with some virus, bacteria, or helminth, e.g., human papillomavirus, Helicobacter pylori, and Schistosoma haematobium that cause cervical, stomach, and urinary bladder cancer, respectively. Certain associations between infection and malignancy are strong and irrefutable; others are still speculative. This article reviews the infectious agents that have been associated with cancer and current knowledge about the mechanisms underlying these associations.     

Ultrasound diagnostics as a method of investigation of plastic induration of the penis.

Using the ultrasound technique of visualization (grey-scale technique) and a method of 'water bath', the authors obtained echograms of plastic indurations of the penis. The echograms can be immediately photographed and interpreted. By their quick, painless and simple performance, without contrast medium and hazardous irradiation, the authors gain an advantage over some other diagnostic methods.     

To freeze or not to freeze embryos: clarity,confusion and conflict

Although embryo freezing is a routine clinical practice, there is little contemporary evidence on how couples make the decision to freeze their surplus embryos, or of their perceptions during that time. This article describes a qualitative study of 16 couples who have had in vitro fertilisation (IVF) treatment. The study question was ‘What are the personal and social factors that patients consider when deciding whether to freeze embryos?’ We show that while the desire for a baby is the dominant drive, couples’ views revealed more nuanced and complex considerations in the decision-making process. It was clear that the desire to have a baby influenced couples’ decision-making and that they saw freezing as ‘part of the process’. However, there were confusions associated with the term ‘freezing’ related to concerns about the safety of the procedure. Despite being given written information, couples were confused about the practical aspects of embryo freezing, which suggests they were preoccupied with the immediate demands of IVF. Couples expressed ethical conflicts about freezing ‘babies’. We hope the findings from this study will inform clinicians and assist them in providing support to couples confronted with this difficult decision-making.