First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase Ⅱ study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m 2 , infused at 10 mg/m 2 per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reducti     

Sexual Function and Distress in Women Treated for Primary Headaches in a Tertiary University Center

IntroductionPrimary headaches are common in women and impact on their quality of life and psychosocial functioning. Few data are available on sexuality in female headache sufferers.AimAn observational pilot study was conducted to assess sexual function and distress in women treated for primary headaches in a tertiary university center.MethodsFrom a total of 194 women consecutively observed over a 3‐month period, 100 patients were recruited. Migraine with and without aura, and tension‐type headache, both episodic and chronic (CTTH), were diagnosed according to the International Classification of Headache Disorders. A detailed pharmacological history was collected, and anxiety and depression were assessed using validated scales. The Female Sexual Function Index (FSFI) and Female Sexual Distress Scale‐Revised were administered.Main Outcome MeasuresThe main outcome measures are sexual symptoms and distress in women treated for primary headaches.ResultsMore than 90% of the women had a median FSFI full‐scale score under the validated cutoff, while 29% reported sexual distress. Hypoactive sexual desire disorder (HSDD) was diagnosed in 20% of the women and the pain domain score (median 2, score range 0–6) was highly affected by the head pain condition. However, the FSFI domain and full‐scale scores did not significantly differ by headache diagnosis. The women with CTTH displayed a high rate of sexual distress (45.5%) and a strong negative correlation between desire, arousal, and full‐scale FSFI score and number analgesics/month (r: ?0.77, P = 0.006; r: ?0.76, P = 0.006; and r: ?0.68, P = 0.02, respectively). Depression was positively correlated with sexual distress (r: 0.63, P = 0.001) only in the women with CTTH.ConclusionWomen treated for primary headaches were found to display a high rate of sexual symptoms and distress. Both migraine and tension‐type headache were associated with sexual pain and HSDD, but women with CTTH seem to be more prone to develop sexual distress. Nappi RE, Terreno E, Tassorelli C, Sances G, Allena M, Guaschino E, Antonaci F, Albani F, and Polatti F. Sexual function and distress in women treated for primary headaches in a tertiary university center. J Sex Med 2012;9:761–769.     

Helicobacter pylori therapy: Present and future

Helicobacter pylori(H.pylori) plays a crucial role in the pathogenesis of chronic active gastritis,peptic ulcer and gastric mucosa-associated lymphoid tissue-lymphoma,and is also involved in carcinogenesis of the stomach.H.pylori treatment still remains a challenge for physicians,since no current first-line therapy is able to cure the infection in all treated patients.Several factors may help in the eradication of therapy failure.We reviewed both bacterial and host factors involved in therapeutic management of the H.pylori infection.In addition,we evaluated data on the most successful therapy regimens-sequential and concomitant therapies-currently available for H.pylori eradication.     

Topical nifedipine with lidocaine ointment versus active control for pain after hemorrhoidectomy: results of a multicentre,prospective, randomized,double-blind study

Background

Spasm through the internal anal sphincter is one of the supposed causes for pain after hemorrhoidectomy, a common and distressing experience. We hypothesized that the addition of topical nifedipine to lidocaine would improve pain control by causing a relaxation of the smooth muscle of the internal anal sphincter.

Methods

We conducted a multicentre randomized, double-blind trial to compare the efficacy of 0.3% nifedipine and 1.5% lidocaine ointment versus 1.5% lidocaine ointment alone in reducing pain after hemorrhoidectomy. A physician unaware of the treatment arm measured pain by use of the Analogue Chromatic Continuous Scale (ACCS) at baseline; soon after surgery; at 2, 4, 6, 8 and 24 hours after surgery; on day 7 after surgery; and at a final visit 14 days after surgery. The physician also noted the time to first analgesic administration within 24 hours after surgery.

Results

In all, 135 patients per group participated (270 total). Evaluation of the delta ACCS score versus basal value, a covariate for rescue analgesic administration time, revealed better pain control in the group that received nifedipine with lidocaine at 6 hours after surgery and on day 7 (p < 0.011 and p < 0.054, respectively). We noticed no difference between groups for time of administration of rescue analgesic, blood pressure, heart rate or frequency of headache.

Conclusion

Although there was no difference between groups for time of administration of rescue analgesic after open hemorrhoidectomy, the patients’ assessment of pain using ACCS showed that the use of topical nifedipine with lidocaine may provide a slight significant difference in favour of the study group at 6 hours and at day 7 after surgery. Narcotic analgesics and nonsteroidal anti-inflammatory drug administration should continue to be recommended. Further research focusing on these outcomes is warranted.     

Third-line sorafenib after sequential therapy with sunitinib and mTOR inhibitors in metastatic renal cell carcinoma

Background

Sunitinib and everolimus have been approved for first- and second-line treatment, respectively, in metastatic renal cell carcinoma (mRCC). The role of sorafenib, which is approved for second-line treatment after cytokines failure, is presently to be defined.

Objective

To determine whether third-line sorafenib after sequential use of sunitinib and mammalian target of rapamycin inhibitors (everolimus or temsirolimus) is feasible and effective.

Design, setting, and participants

One hundred fifty medical records of patients with mRCC treated with first-line sunitinib between January 2006 and January 2010 were reviewed at four participating centers. Data regarding patients treated with the sequence sunitinib–everolimus or temsirolimus–sorafenib were extracted. Central analysis of radiographic images was performed using RECIST criteria to determine progression-free survival (PFS) and overall response rate (oRR) to sorafenib treatment.

Measurements

PFS and oRR to sorafenib were the primary end points. Secondary outcomes were safety and overall survival (OS).

Results and limitations

Thirty-four patients were eligible for the study. A median PFS of 4 mo (range: 3–6 mo) and a median OS of 7 mo since sorafenib treatment (range: 6–10 mo) were reported. Of the patients, 23.5% showed response to sorafenib, with an overall disease control rate (complete responses plus partial responses plus stable disease) of 44%. Selection bias, data incompleteness, and absence of study design are inevitable limitations of the study, although central review can strengthen the quality of presented data.

Conclusions

Third-line sorafenib appears to be active and well tolerated in mRCC after first-line sunitinib and second-line everolimus or temsirolimus, with no patients interrupting sorafenib because of toxicity or lack of compliance. Prospective, placebo-controlled trials are completely lacking and are required in this setting.     

Arthroscopic vs mini-open rotator cuff repair. A quality of life impairment study

We compared the clinical and quality of life related outcome of rotator cuff repair performed using either a mini-open or an arthroscopic technique for rotator cuff tears of less than 3 cm. The records of 64 patients who underwent rotator cuff repair between September 2003 and September 2005 were evaluated. Thirty-two patients underwent a mini-open rotator cuff repair, and 32 patients underwent an arthroscopic rotator cuff repair. The mean follow-up period was 31 months in the mini-open group and 30.6 months in the arthroscopic group (P > 0.05). The UCLA rating system, range of motion examination and the self-administered SF-36 used for postoperative evaluation showed a statistically significant improvement from the preoperative to the final score for both groups (P < 0.05). No statistically significant difference in the total UCLA scores was found when comparing the two repair techniques (P > 0.05). This study suggests that there is no difference in terms of subjective and objective outcomes between the two surgical procedures studied if patients have rotator cuff tears of less than 3 cm.