Phase Ib with expansion study of olaparib plus weekly (Metronomic) carboplatin and paclitaxel in relapsed ovarian cancer patients.

Objective: Our goals were to: establish the maximum-tolerated dose of olaparib tablets combined with metronomic carboplatin and paclitaxel in patients with relapsed high-grade serous ovarian cancer; evaluate dose-limiting toxicities; and evaluate efficacy at the maximum tolerated dose.

Methods: In this open-label, single-arm, investigator-initiated trial (ClinicalTrials.gov NCT01650376), patients with high-grade serous ovarian cancer who failed primary platinum and taxane therapy received oral olaparib tablets twice daily days 1-3 each week combined with fixed-dose metronomic carboplatin AUC2 and paclitaxel 60 mg/m weekly for 3 out of 4 weeks.

A phase I trial of intraperitoneal nab-paclitaxel in the treatment of advanced malignancies primarily confined to the peritoneal cavity.

Purpose: To evaluate intraperitoneal (IP) nab-paclitaxel in patients with advanced malignancies that are primarily confined to the peritoneal cavity in a phase I trial.

Methods: Using a 3 + 3 dose escalation of IP nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, we evaluated six dose levels (35-175 mg/m/dose). Maximum tolerated dose (MTD) and pharmacokinetics (PK) of IP nab-paclitaxel were determined.

Colorectal Chemoprevention Pilot Study (SWOG-9041), randomized and placebo controlled: the importance of multiple luminal lesions.

Background: Colorectal cancer is common worldwide and chemoprevention has the potential of reducing the number of individuals who may suffer and perish from this disease.

Methods: A randomized placebo controlled pilot study in colorectal cancer patients was performed using calcium carbonate as the test agent in a multi-institutional oncology study group.

Results: Two hundred twenty volunteers were randomized in the study.

Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205.

Purpose: Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy.

The board's role in managing a crisis.

In a time of crisis, the board's first responsibility is reassuring the community.

Southwest Oncology Group Trial S9912: intraperitoneal cisplatin and paclitaxel plus intravenous paclitaxel and pegylated liposomal doxorubicin as primary chemotherapy of small-volume residual stage III ovarian cancer.

Objective: While primary cisplatin-based intraperitoneal chemotherapy has been shown to favorably impact survival in small-volume residual advanced ovarian cancer, there is a need to develop strategies that improve the effectiveness of this approach.

Methods: A multi-center phase 2 trial was conducted that added intravenous pegylated liposomal doxorubicin (day 8; 30-40 mg/m(2)) to a regimen of intraperitoneal cisplatin (day 2; 75 mg/m(2)) and intravenous (day 1; 135 mg/m(2)) plus intraperitoneal (day 8; 60 mg/m(2)) paclitaxel. Treatment was initially delivered on an every 3-week schedule, but was modified to an every 4-week program due to excessive toxicity.

Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group-directed intergroup trial S9003.

The survival of patients with Waldenstrom macroglobulinemia (WM) varies enormously. The development of prognostic models in WM has been fraught by limited follow-up in current studies. Here, we update the outcome of a prospective WM trial with a median follow-up of 10 years for live patients.

External beam irradiation and the combination of cisplatin and carmustine followed by carmustine alone for the treatment of high-grade glioma: a phase 2 Southwest Oncology Group trial.

Background: The poor prognosis reported for patients with high-grade glial neoplasms indicates a need for the development of multimodality therapeutic approaches. The addition of chemotherapy has contributed variably to increased survival. The objective of the current study (Southwest Oncology Group [SWOG] 9016) was to determine whether concurrent radiotherapy and chemotherapy with the combination of carmustine and cisplatin could be given safely in a cooperative group setting.

Treatment options for muscle-invasive urothelial cancer for patients who were not eligible for cystectomy or neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin: report of Southwest Oncology Group Trial 8733.

Background: Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients.

Methods: Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function.

A phase II study of cisplatin preceded by a 12-h continuous infusion of concurrent hydroxyurea and cytosine arabinoside (Ara-C) for adult patients with malignant gliomas (Southwest Oncology Group S9149).

Inhibition of DNA excision repair can modulate resistance to cisplatin. Cytosine arabinoside (Ara-C) and hydroxyurea (HU), in combination, inhibit the excision-repair system and removal of platinum-DNA adducts. Marked cytotoxic synergy had been demonstrated in vitro at clinically achievable levels.

Patient training in cancer pain management using integrated print and video materials: a multisite randomized controlled trial.

Standard guidelines for cancer pain treatment routinely recommend training patients to reduce barriers to pain relief, use medications appropriately, and communicate their pain-related needs. Methods are needed to reduce professional time required while achieving sustained intervention effectiveness. In a multisite, randomized controlled trial, this study tested a pain training method versus a nutrition control.

Phase II study of erlotinib in patients with malignant pleural mesothelioma: a Southwest Oncology Group Study.

Purpose: Malignant pleural mesothelioma (MPM) expresses high levels of epidermal growth factor receptor (EGFR), and preclinical studies have identified antitumor activity of EGFR tyrosine kinase inhibitors (TKIs) in MPM. We conducted a phase II trial of the EGFR TKI erlotinib in previously untreated patients with MPM.

Patients And Methods: Patients with measurable and nonmeasurable disease were treated with erlotinib 150 mg/d on days 1 through 28 of each 28-day dosing cycle.

Pay, working conditions, and teacher quality.

Eric Hanushek and Steven Rivkin examine how salary and working conditions affect the quality of instruction in the classroom. The wages of teachers relative to those of other college graduates have fallen steadily since 1940. Today, average wages differ little, however, between urban and suburban districts.

Long-term safety of intravenous ibandronic acid for up to 4 years in metastatic breast cancer: an open-label trial.

Background And Objective: Despite their widespread use in metastatic bone disease, some bisphosphonate drugs are associated with adverse events (AEs), particularly renal toxicity, adding to treatment burdens and increasing healthcare costs. Ibandronic acid is a single-nitrogen bisphosphonate with high efficacy against bone events and metastatic bone pain, and a renal safety profile compar- able to that of placebo. In this study, the safety of ibandronic acid was examined over a period of 4 years.

A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) ixabepilone, in patients with advanced pancreas cancer: a Southwest Oncology Group study.

Purpose: The purpose of this Phase II multi-institutional study was to define the efficacy and toxicity of ixabepilone in patients with advance pancreatic adenocarcinoma.

Patients And Methods: Patients were required to have pancreatic adenocarcinoma and metastatic or recurrent disease that was not amenable to curative resection. Performance status was 0-1, and patients could not have had prior chemotherapy, or chemoradiation therapy for their advanced disease although prior local palliative radiation was allowed.

Phase II trial of R115777 (NSC #70818) in patients with advanced colorectal cancer: a Southwest Oncology Group study.

Purpose: The purpose of this Phase II multi-institutional trial was to determine the efficacy and toxicity of R115777 in previously untreated patients with metastatic colorectal carcinoma.

Patients And Methods: Patients were required to have histologically confirmed colorectal cancer with distant metastatic disease that was not surgically curable. They could not have received prior chemotherapy for metastatic disease.

Progress in ovarian cancer research: proceedings of the 5th Biennial Ovarian Cancer Research Symposium.

Ovarian cancer remains the most lethal gynecological malignancy. The 5th Biennial Symposium overviewed the progress of ovarian cancer research over the last few years. Molecularly based technologies have allowed the identification of multiple biomarkers to aid in ovarian cancer diagnosis and treatment.

Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102.

Purpose: We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF) in node-negative breast cancer patients with and without tamoxifen (TAM), overall and by hormone receptor (HR) status.

Patients And Methods: Node-negative patients identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n = 2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT). Cox regression evaluated overall survival (OS) and disease-free survival (DFS) for CAF versus CMF and TAM versus no TAM separately.

Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-hour infusion (SWOG 9714): a Southwest Oncology Group study.

Background: There are no published prospective trials of chemotherapy for advanced bronchioloalveolar carcinoma (BAC), a subtype of non-small-cell lung cancer for which there is no current standard therapy. This phase II study assesses the efficacy and toxicity of 96-h paclitaxel in chemotherapy-naive patients with advanced BAC.

Patients And Methods: Patients with histologically confirmed stage IIIB (with pleural effusion) or stage IV BAC were eligible.

Phase II trial of oral rubitecan in previously treated pancreatic cancer patients.

Background: Additional systemic treatments for locally advanced or metastatic pancreatic cancer are needed, as current treatment options produce only modest survival benefits. Rubitecan (Orathecin; Supergen Inc., Dublin, CA, http://www.

Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous infusion and levamisole for adjuvant treatment of stage III and high-risk stage II colon cancer.

Purpose: Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer.

Patients And Methods: After surgery, patients were randomly assigned to CIFU 250 mg/m(2)/d for 56 days every 9 weeks for three cycles or FU 425 mg/m(2) and LV 20 mg/m(2) daily for 5 days every 28 to 35 days for six cycles.

Phase II study of CT-2103 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.

Purpose: To evaluate the safety and efficacy of CT-2103, a novel conjugate of paclitaxel and poly-L-glutamic acid, in heavily pretreated patients with recurrent ovarian, fallopian tube, or peritoneal cancer.

Patients And Methods: Ninety-nine patients with measurable disease received intravenous CT-2103 at 175 mg/m2 of conjugated paclitaxel over 10 minutes every 3 weeks without routine premedications. Platinum-sensitive (n = 42) and platinum-refractory or platinum-resistant patients (n = 57) were enrolled.

Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer.

Purpose: To assess oregovomab as consolidation treatment of advanced ovarian cancer and refine the immunotherapeutic strategy for subsequent study.

Patients And Methods: Patients with stage III/IV ovarian cancer who had a complete clinical response to primary treatment were randomly assigned to oregovomab or placebo administered at weeks 0, 4, and 8, and every 12 weeks up to 2 years or until recurrence. The primary end-point was time to relapse (TTR).

Determinants of gating polarity of a connexin 32 hemichannel.

There is good evidence supporting the view that the transjunctional voltage sensor (V(j)-sensor) of Cx32 and other Group 1 connexins is contained within a segment of the N-terminus that contributes to the formation of the channel pore. We have shown that the addition of negatively charged amino acid residues at several positions within the first 10 amino acid residues reverses the polarity of V(j)-gating and proposed that channel closure is initiated by the inward movement of this region. Here, we report that positive charge substitutions of the 2nd, 5th, and 8th residues maintain the negative polarity of V(j)-gating.