Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study.

PURPOSE: In HER2-positive breast cancer (HER2+ BC), neoadjuvant chemotherapy (NACT) with dual HER2-targeted therapy achieves high pathologic complete response (pCR) rates. Anthracycline-free NACT regimens avoid toxicities associated with anthracyclines, but every 3-week TCHP also has substantial side effects. We hypothesized that a weekly regimen might have equivalent efficacy with less toxicity; we also investigated whether poorly responding patients would benefit from switching to AC. METHODS: Patients with clinical stage II-III HER2+ BC received weekly paclitaxel 80 mg/m2 and carboplatin AUC2 with every 3-week trastuzumab and pertuzumab (wPCbTP), with the option of splitting the pertuzumab loading dose. After 12 weeks, responding patients continued wPCbTP for another 6 weeks, while non-responders switched to AC. Dose modifications and post-op therapy were at investigator discretion. RESULTS: In 30 evaluable patients, the pCR rate was 77% (95% CI 58-90%); 12/14 (86%) in ER-negative and 11/16 (69%) in ER-positive. Only two patients transitioned to AC for non-response, of which one achieved pCR. There were no episodes of febrile neutropenia or grade ≥ 3 peripheral neuropathy, though several patients who continued wPCbTP stopped before week 18. Split-dose pertuzumab was associated with less grade ≥ 2 diarrhea (40%) than the standard loading dose (60%). CONCLUSION: pCR rates with our regimen were as high as reported with TCHP with fewer grade ≥ 3 toxicities, though diarrhea remains a concern. Too few patients had a suboptimal response to adequately test switching to AC. The wPCbTP regimen should be considered an alternative to TCHP as neoadjuvant therapy for HER2+ BC. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT02789657.

Perforated peptic ulcer. Determinants of morbidity and mortality.

A review of 109 patients with perforated peptic ulcer revealed a sex ratio of 60:49, male:female, with mean age of 67 (76 patients greater than or equal to age 50). Peritoneal cultures were positive in 52 per cent, with the most common organisms streptococci and fungi. Subsequent infectious morbidity with these organisms was rare. Postoperative respiratory and renal failure were associated with intraoperative hypotension (systolic pressure less than 90 mm Hg). Mortality was associated with age greater than 55 and intraoperative hypotension. We conclude that in the 1980s perforated peptic ulcer occurs most frequently in older patients and that acid stomach contents does not ensure sterility, yet subsequent infectious morbidity is rare. Intraoperative hypotension, which occurs especially in patients greater than 55 years, results in significant morbidity and mortality. Attention to preoperative and intraoperative resuscitation is the single most effective therapy for reducing morbidity and mortality from this disease.