Multicenter phase II study on cisplatin, pemetrexed, and bevacizumab followed by maintenance with pemetrexed and bevacizumab for patients with advanced or recurrent nonsquamous non-small cell lung cancer: MAP study.

BACKGROUND: We evaluated the safety and efficacy of induction chemotherapy with bevacizumab followed by maintenance chemotherapy with bevacizumab for advanced non-small cell lung cancer (NSCLC) in this multicenter phase II study. METHODS: Chemotherapy-naïve patient with stage IIIB-IV or recurrent nonsquamous NSCLC were eligible. We planned approximately four cycles of induction cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) followed by maintenance with pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) until disease progression. Progression-free survival (PFS) was the primary endpoint. RESULTS: Forty patients received a median of four induction chemotherapy cycles. Of them, 35 (87.5%) patients received a median of nine maintenance chemotherapy cycles. The objective response was 70.6%, and the disease control rate was 97.1%. The median PFS was 10.8 (95% CI, 9.0-12.6), and overall survival was 48.0 (95% CI, 32.9-63.1) months. Median PFS of 23 patients with epidermal growth factor receptor (EGFR) mutations and of 16 patients without EGFR mutations were 12.9 (95% CI, 9.4-16.3) and 7.9 (95% CI, 1.1-14.7) months, respectively. Toxicities graded ≥3 included neutropenia (15%), anemia (15%), hypertension (7.5%), anorexia (7.5%), fatigue (7.5%), thromboembolic events (5%), jaw osteonecrosis (5%), nausea (2.5%), oral mucositis (2.5%), tumor pain (2.5%), hyponatremia (2.5%), and gastrointestinal perforation (2.5%). Treatment-related deaths were not found. CONCLUSIONS: In patients with advanced or recurrent nonsquamous NSCLC, induction chemotherapy with cisplatin, pemetrexed, and bevacizumab followed by maintenance chemotherapy with pemetrexed and bevacizumab is safe and effective regardless of their EGFR mutation status. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000005569 . Registered date: May 8, 2011.

Impact of oral hygiene on febrile neutropenia during breast cancer chemotherapy.

PURPOSE: Oral hygiene is crucial in the management of oral and febrile complications during chemotherapy for cancer. This study aimed to investigate the impact of oral hygiene on the incidence of febrile neutropenia (FN) throughout the course of chemotherapy for breast cancer. METHODS: A total of 137 patients with breast cancer who underwent four cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide (TC) combination therapy or docetaxel alone were assessed for oral hygiene by quantifying the number of oral bacteria they harbored. These patients received professional oral health care (POHC). Eighteen patients underwent primary prophylaxis with granulocyte colony-stimulating factors. The relationship between oral bacteria count and FN incidence was retrospectively assessed. RESULTS: The FN incidence rate was 47.4% throughout all treatment cycles (32.8%, 13.5%, 14.3%, and 14.4% in cycles 1, 2, 3, and 4, respectively). The oral bacteria count decreased with each treatment cycle (cycle 1: 9.10 × 106 colony-forming units (CFU)/mL, cycle 2: 5.89 × 106 CFU/mL, cycle 3: 4.61 × 106 CFU/mL, cycle 4: 5.85 × 106 CFU/mL, P = 0.004). Among 281 treatment cycles, FN occurred in 63 (22.4%). In the treatment cycle-based analysis, high oral bacteria count was an independent risk factor for FN. CONCLUSION: FN incidence decreased with each treatment cycle and was associated with changes in oral bacteria counts. The oral bacterial count was one of risk factors for FN development in breast cancer.

Successful management of multiple esophagorespiratory fistulas using two types of stent: report of a case.

We herein describe a 41-year-old man with esophageal cancer who developed three esophagorespiratory fistulas (ERFs) that were successfully treated using one esophageal and three airway stents. A self-expandable metallic stent (SEMS) was initially inserted into the esophagus to close an ERF in the right bronchus. However, two new ERFs developed in the trachea and the left main bronchus 3 months later because of pressure necrosis and penetration of the esophageal SEMS. These secondary ERFs were subsequently closed using two silicone stents, together with one SEMS in the airway. This experience suggests that appropriate stenting can control multiple and large ERFs.

Prospective feasibility study of sealing pulmonary vessels with energy in lung surgery.

OBJECTIVE: Vascular sealing with an energy vessel sealing system during lung resection may allow surgeons to treat small vessels with minimal dissection, possibly decreasing likelihood of injury. Few large prospective trials have examined the proximal sides of vessels not ligated in addition to sealing during surgery. We therefore assessed feasibility of an energy device to seal pulmonary artery and vein branches without further ligation. METHODS: This prospective, preoperative registration study at 2 institutions evaluated safety of energy sealing with the LigaSure (Medtronic, Minneapolis, Minn), with no additional reinforcing material such as suture ligation, for pulmonary vessels as large as 7 mm during anatomic lung resection (cohort 1 study). A postoperative hemorrhage occurred in the 128th case, so a cohort 2 study proceeded after we changed inclusion criterion for pulmonary arteries from a maximum of 7 mm to a maximum of 5 mm. RESULTS: In cohort 1 (n = 128) and cohort 2 (n = 200), 216 and 250 pulmonary arteries and 189 and 213 pulmonary veins, respectively, were treated with energy sealing. Overall postoperative hemorrhage rate was 0.3% (1/328 patients); however, no serious postoperative complications were associated with energy sealing among the 200 patients in cohort 2. Subsequent inspection of the torn artery stump confirmed that the bleeding in the 128th case was in an area adjacent to the sealing zone. CONCLUSIONS: Energy sealing without reinforcement allows secure treatment during lung resection of pulmonary arteries as large as 5 mm in diameter and pulmonary veins as large as 7 mm.

Bevacizumab with Single-agent Chemotherapy in Previously Treated Non-squamous Non-small-cell Lung Cancer: Phase II Study.

AIM: This study was designed to evaluate the efficacy and tolerability of bevacizumab with docetaxel or pemetrexed in previously treated patients with non-squamous non-small cell lung cancer. PATIENTS AND METHODS: This study enrolled patients who had received at least one chemotherapy regimen, regardless of prior use of bevacizumab. Combinations of docetaxel or pemetrexed were chosen by attending physicians. The primary endpoint was progression-free survival, and secondary endpoints were safety, disease control rate, and overall survival. RESULTS: Thirty patients from two institutions were eligible. The median progression-free and overall survival were 5.0 months (95% confidence interval=3.2-8.8 months) and 15.8 months (95% confidence interval=10.5-19.6 months), respectively. The disease control rate was 66.7%. Treatments were well tolerated, but the development rate of osteonecrosis of the jaw was 10%. CONCLUSION: Addition of bevacizumab in a salvage setting might be effective, but the development of osteonecrosis of the jaw needs to be monitored.

Advantage of absorbable suture material for pulmonary artery ligation.

PURPOSE: The applicability of absorbable materials as ligatures of pulmonary vessels has not been described. The present study compares tissue reactions around sites of pulmonary arteries ligated with absorbable material (Vicryl) and with nonabsorbable material (silk). METHODS: Beagle dogs underwent thoracotomy and the pulmonary artery branches were ligated with silk or Vicryl under general anesthesia. The ligated arterial tissues were obtained at 4 and 8 weeks after thoracotomy and processed for pathological analysis. RESULTS: The arteries ligated using Vicryl or silk were clinically completely sealed at 4 weeks after ligation. More inflammation and granuloma were evident at tissues surrounding ligations made with silk than with Vicryl at 8 weeks. Hyperplasia of the arterial intima continued at 8 weeks after ligation with both Vicryl and silk sutures, although some hyperplasia similar to that in nonligated arterial intima appeared at 4 weeks after ligation. CONCLUSION: Less inflammation and granuloma are caused at arterial tissues around ligations accomplished with absorbable Vicryl than those done with nonabsorbable silk sutures, although both are equally effective. Absorbable sutures might be suitable for ligating pulmonary arteries.