An open-label, single-arm, phase 2 trial of panitumumab plus FOLFIRI as second-line therapy in patients with metastatic colorectal cancer.

BACKGROUND: This prospective analysis evaluated the effect of tumor KRAS status on efficacy of second-line panitumumab plus folinic acid/5-fluorouracil/irinotecan (FOLFIRI). METHODS: This phase 2, open-label, single-arm study enrolled patients with unresectable, measurable metastatic colorectal cancer (mCRC) after failure of first-line treatment with oxaliplatin-based chemotherapy plus bevacizumab. Patients received panitumumab 6 mg/kg plus FOLFIRI every 2 weeks until disease progression or intolerability. Tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) were performed by the investigators every 8 weeks from weeks 8-32 and every 12 weeks thereafter. KRAS status was determined by real-time polymerase chain reaction (PCR) on DNA extracted from fixed tumor sections. Efficacy endpoints included objective response rate, progression-free survival (PFS), and overall survival (OS). Safety endpoints included incidence of adverse events (AEs). Endpoints were evaluated by tumor KRAS status. RESULTS: Of 116 patients enrolled, 109 patients with known tumor KRAS status received treatment; 59% had wild-type KRAS, and 41% had mutant KRAS. Fifteen patients (23%) with wild-type KRAS and 7 patients (16%) with mutant KRAS had a complete or partial response to treatment. Median PFS was 26 weeks (95% CI, 19-33 weeks) and 19 weeks (95% CI, 12-25 weeks) in the wild-type KRAS and mutant KRAS strata, respectively. Median OS was 50 weeks (95% CI, 39-76 weeks) and 31 weeks (95% CI, 23-47 weeks) in wild-type KRAS and mutant KRAS strata, respectively. Skin-related toxicities (86% of all patients) and diarrhea (74%) were the most common AEs. CONCLUSION: Panitumumab plus FOLFIRI numerically improved objective response rate, PFS, and OS in favor of patients with wild-type KRAS tumors. The safety profile was consistent with panitumumab plus FOLFIRI trials in similar patient populations.

Laparoscopy-assisted reconstruction of a long-segment ureteral stricture using reconfigured ileal segment: application of the Yang Monti principle.

We report the first laparoscopy-assisted replacement of the ureter with an ileal segment reconfigured by using the Yang Monti principle. We performed this surgery in a patient with a long segment right lower ureteral stricture from a nonspecific cause. The initial dissection of the colon and the ureter was done laparoscopically. The bowel was identified and delivered through a 3.5 cm midline infraumbilical incision. The bowel segment was isolated and reconfigured extracorporeally. The bowel was placed back in the peritoneal cavity, and the ureteroileal and the ileovesical anastomosis were performed using the laparoscopic intracorporeal suturing technique. The patient had an uneventful postoperative recovery. The ileal segment showed good patency on early follow-up.

Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer.

PURPOSE: The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS). PATIENTS AND METHODS: Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy. RESULTS: Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure. CONCLUSION: At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.

Laparoscopy-assisted ileal ureter creation for multiple tuberculous strictures: report of two cases.

We describe in detail the technique of laparoscopy-assisted ileal ureter creation for multiple tuberculous ureteral strictures in two patients. The proximal anastomosis included an ileocalicostomy in the first patient and an ileopyelostomy in the second patient. The first patient had bowel entrapment behind the mesentery of the ileal loop, but the second patient had an uneventful postoperative recovery. Short-term follow-up showed good patency of the ileal loop. The variations in the technique that can cause postoperative problems are discussed, and the future of this technique is postulated.

Phase II trial of weekly docetaxel/ gemcitabine as first-line chemotherapy in patients with locally recurrent or metastatic breast cancer.

PURPOSE: A phase II study evaluated weekly docetaxel/gemcitabine as first-line chemotherapy for locally recurrent or metastatic breast cancer in a multicenter community oncology practice setting. PATIENTS AND METHODS: Eligible patients who had not received chemotherapy for metastatic disease received docetaxel 30 mg/m2 followed by gemcitabine 800 mg/m2, each administered weekly for 3 weeks (days 1, 8, and 15), followed by a 1-week rest period (28-day cycle). Patients also received oral dexamethasone to reduce the incidence/severity of fluid retention and hypersensitivity reactions. Of the 46 enrolled patients, 45 were treated as part of the intent-to-treat (ITT) population and were evaluable for safety. RESULTS: There were 3 complete responses and 12 partial responses among the 39 evaluable patients, for an objective response rate (ORR) of 39% (95% confidence interval [CI], 24%-54%). The ORR in the ITT population was 33% (95% CI, 18%-48%). Median time to response was 3.4 months, with a median response duration of 6.7 months. Median survival was 15.8 months, and median time to progression was 5.8 months. The most common grade 3/4 hematologic toxicity was neutropenia (13.3%); there was a low incidence of other grade 3/4 hematologic toxicities. Grade 3 fatigue (15.6%) was the most common grade 3/4 nonhematologic toxicity, and grade 2 alopecia occurred in 47% of patients. One patient who had been receiving chronic corticosteroid therapy died from treatment-related neutropenia and acute respiratory distress syndrome. CONCLUSION: These phase II results suggest that weekly docetaxel/gemcitabine is moderately active and well tolerated as first-line therapy for locally recurrent or metastatic breast cancer. No clear advantage for combined weekly docetaxel/gemcitabine was observed compared with published results on the efficacy of docetaxel and gemcitabine given as single agents.

Laparoscopic extravesical ureteral reimplantation in adults using intracorporeal freehand suturing: report of two cases.

BACKGROUND AND PURPOSE: Laparoscopic extravesical neoureterocystostomy is an infrequently described technique in adults. It is a technically demanding procedure, especially when the intracorporeal freehand suturing technique is used. Our aim is to describe two cases where we used the intracorporeal freehand suturing technique successfully for performing laparoscopic extravesical transperitoneal ureteral reimplantation. We describe the preliminary results of these cases. PATIENTS AND METHODS: We performed this surgery in two female patients. The first patient had a low ureterovaginal fistula after abdominal hysterectomy. We performed a laparoscopic extravesical neoureterocystostomy by the refluxing technique. The second patient had a lower-third ureteral stricture. We performed a laparoscopic extravesical neoureterocystostomy with detrusorrhaphy and supported it with a psoas hitch. RESULTS: The average surgical time was 235 minutes. The average blood loss was 50 mL. The average stay was 48 hours, and the average time to starting oral intake was 12 hours. The average requirement for postoperative analgesia was one injection of diclofenac sodium, followed by oral ibuprofen. Follow-up urography showed good clearance of the kidney and ureter. The second patient, in whom the detrusorrhaphy was performed, did not show any reflux on the postoperative cystogram. CONCLUSION: Laparoscopic extravesical neoureterocystostomy using intracorporeal freehand suturing technique, combining detrusorrhaphy and psoas hitch, is a feasible procedure in adults for various indications. The detrusorrhaphy was effective in preventing reflux, but the long-term results need to be evaluated.

Laparoscopic pyelolithotomy--a technique for the management of stones in the ectopic pelvic kidney.

We present our preliminary experience with the technique of laparoscopic pyelolithotomy for ectopic pelvic kidney calculi. This surgery has low morbidity and is ideally suited for the ectopic pelvic kidney with a laterally or anteriorly directed pelvis.