Helen J Ross

Mayo Clinic - Scottsdale, Scottsdale, Arizona, United States

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Publications (31)136.72 Total impact

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    ABSTRACT: Introduction: PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Methods: Patients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m2, carboplatin, area under the curve = 6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m2, carboplatin, area under the curve = 6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed. Results: Baseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7–1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms. Conclusions: Pem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2014; 10(1). DOI:10.1097/JTO.0000000000000366 · 5.80 Impact Factor
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    ABSTRACT: Objective This randomized phase II study assessed the efficacy and safety of obatoclax mesylate, a small-molecule Bcl-2 inhibitor, added to carboplatin/etoposide chemotherapy as initial treatment for extensive-stage small-cell lung cancer (ES-SCLC). Materials and Methods Chemotherapy-naïve subjects with ES-SCLC and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 received carboplatin/etoposide with (CbEOb) or without (CbE) obatoclax for up to six cycles. Responders to CbEOb could receive maintenance obatoclax until disease progression. The primary endpoint was objective response rate (ORR). Results 155 subjects (median age 62, 58% male, 10% ECOG PS 2) were treated with CbEOb (n = 77) or CbE (n = 78); 65% and 59% of subjects, respectively, completed six cycles. ORR was 62% with CbEOb versus 53% with CbE (1-sided p = 0.143). Clinical benefit (ORR+ stable disease) trended better with CbEOb (81% versus 68%; p = 0.054). Median progression-free survival (PFS) and overall survival (OS) were 5.8 months (95% confidence interval [CI]: 5.3-6.5) and 10.5 months (8.9-13.8) with CbEOb and 5.2 months (95% CI: 4.1-5.7) and 9.8 months (7.2-11.2) with CbE. Median OS was 10.5 months (95% CI: 8.9-13.8) and 9.8 months (7.2-11.2) with a nonsignificant hazard ratio for OS, 0.823; 1-sided p = 0.121. Grade 3/4 adverse events (AEs) were primarily hematologic and similar in frequency between treatment arms. Obatoclax-related somnolence and euphoria were grade 1/2, transient, and did not require treatment discontinuation. Conclusion Obatoclax was well tolerated when added to carboplatin/etoposide in first-line treatment of ES-SCLC, but failed to significantly improve ORR, PFS, or OS. Clinical Trial Registration NCT00682981
    Lung Cancer 09/2014; 85(3). DOI:10.1016/j.lungcan.2014.05.003 · 3.74 Impact Factor
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    ABSTRACT: We hypothesized that the combination of bevacizumab, carboplatin, and pemetrexed will be an effective first-line regimen in fit, elderly patients with nonsquamous non-small-cell lung cancer.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2014; 9(8):1146-1153. DOI:10.1097/JTO.0000000000000217 · 5.80 Impact Factor
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    ABSTRACT: Minimally invasive esophagectomy (MIE) is accepted for resection of early esophageal cancers. The optimal surgical approach for more advanced disease is unknown. An evaluation of MIE in patients with advanced tumors having undergone neoadjuvant chemoradiotherapy (nCRT) is presented. A retrospective review of patients with esophageal cancer who underwent MIE from November 2006 to November 2011 was performed RESULTS: In total, 96 consecutive patients underwent MIE for malignancy. Median age was 65 years (range 26 to 88), and 86% were male. Adenocarcinoma represented 87% of patients. Eighty-three percent of patients were staged IIa or higher and 62 (65%) patients received neoadjuvant chemoradiotherapy. Four (6%) patients additionally received intraoperative electron beam radiotherapy. Twenty-six (27%) patients received postoperative adjuvant therapy with 22 (85%) of these having also received neoadjuvant chemoradiotherapy. All cases were completed thoraco-laparoscopically except for 2 conversions to mini-laparotomy. Twelve (12%) cervical anastomoses and 84 (88%) thoracic anastomoses were performed. Median operative time was 326 minutes (range 193 to 567) and did not differ significantly between those with and without nCRT. Complete pathologic response was seen in 21 (34%) of the 62 patients receiving neoadjuvant treatment. Major and minor morbidities were experienced in 28% and 38.5% of patients. There were 2 (2%) in-hospital mortalities; 1 each having received or not received neoadjuvant therapy. At median follow-up 24 months (range 3 to 70 months), overall survival was 58% and 55 (57%) patients were alive without recurrence. Minimally invasive esophagectomy is an acceptable surgical therapy for advanced-stage esophageal malignancies after nCRT without evidence for increased morbidity or mortality.
    The Annals of thoracic surgery 11/2013; 97(2). DOI:10.1016/j.athoracsur.2013.09.042 · 3.65 Impact Factor
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    ABSTRACT: INTRODUCTION:: The purpose of this study was to assess the safety and efficacy of gemcitabine and carboplatin with (arm A) or without (arm B) daily oral cediranib as first-line therapy for advanced non-small-cell lung cancer. METHODS:: A lead-in phase to determine the tolerability of gemcitabine 1000 mg/m on days 1 and 8, and carboplatin on day 1 at area under curve 5 administered every 21 days with cediranib 45 mg once daily was followed by a 2 (A):1 (B) randomized phase II study. The primary end point was confirmed overall response rate (ORR) with 6-month progression-free survival (PFS6) rate in arm A as secondary end point. Polymorphisms in genes encoding cediranib targets and transport were correlated with treatment outcome. RESULTS:: On the basis of the safety assessment, cediranib 30 mg daily was used in the phase II portion. A total of 58 and 29 evaluable patients were accrued to arms A and B. Patients in A experienced more grade 3+ nonhematologic adverse events, 71% versus 45% (p = 0.01). The ORR was 19% (A) versus 20% (B) (p = 1.0). PFS6 in A was 48% (95% confidence interval: 35%-62%), thus meeting the protocol-specified threshold of at least 40%. The median overall survival was 12.0 versus 9.9 months (p = 0.10). FGFR1 rs7012413, FGFR2 rs2912791, and VEGFR3 rs11748431 polymorphisms were significantly associated with decreased overall survival (hazard ratio 2.78-5.01, p = 0.0002-0.0095). CONCLUSIONS:: The trial did not meet its primary end point of ORR but met its secondary end point of PFS6. The combination with cediranib 30 mg daily resulted in increased toxicity. Pharmacogenetic analysis revealed an association of FGFR and VEGFR variants with survival.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2012; 8(1). DOI:10.1097/JTO.0b013e318274a85d · 5.80 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) following open esophagectomy has been associated with increased rates of pulmonary and anastomotic complications, and mortality. This study seeks to evaluate effects of AF after minimally invasive esophagectomy (MIE). A retrospective review of patients consecutively treated with MIE for esophageal carcinoma, dysplasia. and benign disease from November 2006 to November 2011 was performed. One hundred twenty-one patients underwent MIE. Median age was 65 years (range 26-88) with 85% being male. Thirty-eight (31.4%) patients developed AF postoperatively. Of these 38 patients, 7 (18.4%) had known AF preoperatively. Patients with postoperative AF were significantly older than those without postoperative AF (68.7 vs. 62.8 years, P = 0.008) and more likely to be male (94.7% vs. 80.7%, P = 0.04). Neoadjuvant chemoradiation showed a trend toward increased risk of AF (73.7% vs 56.6%, P = 0.07). Sixty-day mortality was 2 of 38 (5.3%) in patients with AF and 4 of 83 (6.0%) in the no AF cohort (P = 1.00). The group with AF had increased length of hospitalization (13.4 days vs. 10.6 days P = 0.02). No significant differences in rates of pneumonia (31.6% vs. 21.7% P = 0.24), stricture (13.2% vs. 26.5% P = 0.10), or leak requiring return to operating room (13.2% vs. 8.4% P = 0.51) were noted between groups. We did not find an increased rate of AF in our MIE cohort compared with prior reported rates in open esophagectomy populations. AF did result in an increased length of stay but was not a predictor of other short-term morbidities including anastomotic leak, pulmonary complications, stenosis, or 60-day mortality. © 2015 International Society for Diseases of the Esophagus.
    Journal of the American College of Surgeons 09/2012; 215(3):S60. DOI:10.1016/j.jamcollsurg.2012.06.170 · 4.45 Impact Factor
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    ABSTRACT: Background This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials. Patients and methods Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared. Results PCI patients survived significantly longer than non-PCI patients {hazard ratio [HR] = 0.61 [95% confidence interval (CI): 0.52-0.72]; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018). Conclusions PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates.
    Annals of Oncology 07/2012; 23(11):2919-2924. DOI:10.1093/annonc/mds123 · 6.58 Impact Factor
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    ABSTRACT: Objectives Concurrent combined modality therapy is optimal treatment for patients with stage III non-small cell lung cancer (NSCLC) and is given with curative intent. However, elderly patients (≥ 75) are often undertreated, despite good performance status (PS). This study evaluated the treatment, outcomes and survival in elderly patients with stage III NSCLC versus patients < 75 years old.Materials and MethodsA retrospective review of data from the Lung Cancer Registry at Mayo Clinic Arizona (MCA) was conducted. Patients with newly diagnosed stage III NSCLC from 1998 to 2006 were analyzed for type of therapy and outcomes.ResultsThree hundred and eighty-nine patients with newly diagnosed stage III NSCLC were identified from 1998 to 2006. Two hundred and forty-three (62%) patients were < 75 years old, and 146 patients (38%) were ≥ 75 years old. Among 374 eligible patients, 45% of patients < 75 years old received combined chemoradiation therapy vs. only 21% of patients ≥ 75 years old (p < 0.0001). The median survival in the < 75 age group was 14.5 months vs. 10.1 months in the ≥ 75 age group (p = 0.0014). In the < 75 age group, median survival was 15.0 months in patients who received combined modality treatment vs. 14.1 months in the other treatments group (p = 0.02). In the elderly group, median survival was 19.9 months in the combined modality group vs. 7.8 months in the other treatments group (p = 0.0048).Conclusion Our results confirm that older patients are less likely to receive optimal therapy, regardless of functional status. Prospective studies are desperately needed to help improve management of the burgeoning geriatric oncology population.
    Journal of Geriatric Oncology 04/2012; 3(2):104–110. DOI:10.1016/j.jgo.2011.12.002 · 1.15 Impact Factor
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    ABSTRACT: Bcl-2 family genes are frequently amplified in small cell lung cancer (SCLC). A phase I trial was conducted to evaluate the safety of obatoclax, a Bcl-2 family inhibitor, given in combination with standard chemotherapy. Eligible patients (3-6 per cohort) had extensive-stage SCLC, measurable disease, ≤ 1 before therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients were treated with escalating doses of obatoclax, either as a 3- or 24-h infusion, on days 1-3 of a 21-day cycle, in combination with carboplatin (area under the curve 5, day 1 only) and etoposide (100 mg m(-2), days 1-3). The primary endpoint was to determine the maximum tolerated dose of obatoclax. Twenty-five patients (56% male; median age 66 years) were enrolled in three dose cohorts for each schedule. Maximum tolerated dose was established with the 3-h infusion at 30 mg per day and was not reached with the 24-h infusion. Compared with the 24-h cohorts, the 3-h cohorts had higher incidence of central nervous system (CNS) adverse events (AEs); dose-limiting toxicities were somnolence, euphoria, and disorientation. These CNS AEs were transient, resolving shortly after the end of infusion, and without sequelae. The response rate was 81% in the 3-h and 44% in the 24-h infusion cohorts. Although associated with a higher incidence of transient CNS AEs than the 24-h infusion, 3-h obatoclax infusion combined with carboplatin-etoposide was generally well tolerated at doses of 30 mg per day. Though patient numbers were small, there was a suggestion of improved efficacy in the 3-h infusion group. Obatoclax 30 mg infused intravenously over 3 h on 3 consecutive days will be utilised in future SCLC studies.
    British Journal of Cancer 02/2012; 106(5):839-45. DOI:10.1038/bjc.2012.21 · 4.82 Impact Factor
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    ABSTRACT: Minimally invasive esophagectomy (MIE) has been performed using a variety of techniques evolving during the past decade. We present our initial experience and outcomes of patients undergoing transthoracic MIE using a circular end-to-side anastomosis created with the transorally directed EEA circular stapler OrVil (Covidien, New Haven, CT). Complications, including anastomotic leak and stricture occurrence, are reviewed. A retrospective review evaluated consecutive patients undergoing MIE for esophageal cancer or related disease with intrathoracic end-to-side anastomoses using the transorally directed EEA circular stapler from December 2007 to May 2010. Medical records were reviewed for demographics, staging, neoadjuvant chemoradiotherapy, comorbidities, adjuvant therapy, complications, and survival. During this period, 51 consecutive patients (84% male; mean age, 65 years) underwent MIE. Neoadjuvant chemoradiotherapy was performed in 32 patients, and 4 had intraoperative radiotherapy. Mean operative time was 338 minutes (range, 211 to 565 minutes), including the 4 patients with intraoperative radiotherapy. Operative time improved with experience (excluding intraoperative radiotherapy) from a mean of 378 minutes (patients 1 to 14) to 300 minutes (patients 37 to 51). Median hospital stay was 11 days (range, 6 to 48 days). Anastomotic leaks occurred in 5 patients (9.8%). Postoperative deaths included 1 in-hospital (2.0%) and 2 (3.9%) after discharge. Stricture was diagnosed and treated in 7 patients (13.7%). Follow-up was a median of 12 months (range, 1 to 31 months). Transthoracic MIE using an end-to-side anastomosis with the transorally directed EEA circular stapler resulted in acceptable stricture and leak rates with good outcomes comparable to published outcomes for open surgical resections.
    The Annals of thoracic surgery 09/2011; 92(5):1862-9. DOI:10.1016/j.athoracsur.2011.07.007 · 3.65 Impact Factor
  • Fuel and Energy Abstracts 11/2010; 78(3). DOI:10.1016/j.ijrobp.2010.07.720
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    ABSTRACT: Southwest Oncology Group 9504 demonstrated the feasibility and potential benefit of docetaxel consolidation after etoposide, cisplatin, and radiotherapy in patients with locally advanced non-small cell lung cancer. Our study assessed consolidation with either gemcitabine alone or with docetaxel after identical chemoradiation as used in Southwest Oncology Group 9504. Patients with stage III non-small cell lung cancer and good performance status were included. Treatment consisted of concurrent cisplatin 50 mg/m on days 1 and 8 plus etoposide 50 mg/m on days 1 to 5 for two 28-day cycles plus radiotherapy (62 Gy, 2 Gy daily in 31 fractions over 7 weeks), followed by randomization to either gemcitabine 1000 mg/m on days 1 and 8 (G) or gemcitabine 1000 mg/m on days 1 and 8 plus docetaxel 75 mg/m on day 1 (GD) every 21 days for three cycles. Eighty-three patients were entered, 81 received induction therapy, and 64 were randomized (32 in each arm). Grade 3 or four events, including neutropenia (56.3% vs. 28.1%, p = 0.03), anemia (18.8% vs. 3.1%, p = 0.05), and fatigue (15.6% vs. 6.3%, p = NS), were more frequent with GD compared with G. Among all patients, median survival from registration was 20.8 months (95% confidence interval: 16.4-33.8), and 2-year survival was 46.7% (95% confidence interval: 35.6-57.1). From randomization, median progression-free survival was 5.4 months for G and 13.4 months for GD, and median survival was 16.1 months for G and 29.5 months for GD. Two-year survival rates were 40.6% for G and 55.7% for GD. The doublet, as expected, resulted in more toxicity, particularly myelosuppression and fatigue. Survival associated with the GD treatment arm of this trial exceeds that of previously reported trials.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2010; 5(5):673-9. DOI:10.1097/JTO.0b013e3181d60e8f · 5.80 Impact Factor
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    ABSTRACT: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival times were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase >or=200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2009; 4(7):869-74. DOI:10.1097/JTO.0b013e3181a9a020 · 5.80 Impact Factor
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    ABSTRACT: The standard of care for resectable gastric or gastroesophageal (GE) junction cancer for patients who can tolerate a surgical procedure is surgical resection, but surgery alone is not optimal treatment for patients at high risk for relapse. For patients with lower-risk lesions (confined to gastric wall, nodes negative; T1-2N0M0), local-regional relapse risks are low, and adjuvant radiotherapy is usually not recommended, except in select instances. Since both local-regional and systemic relapses are common after resection of high-risk gastric or GE junction cancers (beyond wall, nodes positive, or both; T3-4N0, TanyN+), adjuvant treatment is indicated for these patients. The results of phase III trials that demonstrate a survival benefit for adjuvant preoperative radiotherapy, postoperative chemoradiation, or preoperative chemoradiation vs. surgery alone will be presented and compared with the results of adjuvant perioperative chemotherapy. Results of Surveillance, Epidemiology, and End Results (SEER) analyses and meta-analyses that support the role of adjuvant radiotherapy or chemoradiation will be summarized.
    Gastrointestinal cancer research: GCR 04/2009; 3(2 Suppl):S26-32.
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    ABSTRACT: Paclitaxel poliglumex (PPX), a macromolecule drug conjugate linking paclitaxel to polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel. Patients with non-small-cell lung cancer (NSCLC) who had received one prior platinum-based chemotherapy received 175 or 210 mg m(-2) PPX or 75 mg m(-2) docetaxel. The study enrolled 849 previously treated NSCLC patients with advanced disease. Median survival (6.9 months in both arms, hazard ratio=1.09, P=0.257), 1-year survival (PPX=25%, docetaxel=29%, P=0.134), and time to progression (PPX=2 months, docetaxel=2.6 months, P=0.075) were similar between treatment arms. Paclitaxel poliglumex was associated with significantly less grade 3 or 4 neutropenia (P<0.001) and febrile neutropenia (P=0.006). Grade 3 or 4 neuropathy (P<0.001) was more common in the PPX arm. Patients receiving PPX had less alopecia and did not receive routine premedications. More patients discontinued due to adverse events in the PPX arm compared to the docetaxel arm (34 vs 16%, P<0.001). Paclitaxel poliglumex and docetaxel produced similar survival results but had different toxicity profiles. Compared with docetaxel, PPX had less febrile neutropenia and less alopecia, shorter infusion times, and elimination of routine use of medications to prevent hypersensitivity reactions. Paclitaxel poliglumex at a dose of 210 mg m(-2) resulted in increased neurotoxicity compared with docetaxel.
    British Journal of Cancer 06/2008; 98(10):1608-13. DOI:10.1038/sj.bjc.6604372 · 4.82 Impact Factor
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    ABSTRACT: Introduction: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. Methods: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m2/10 min without routine steroid premedication) or paclitaxel (225 mg/m2/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. Results: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). Conclusion: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient.
    Journal of Thoracic Oncology 05/2008; 3(6):623-630. DOI:10.1097/JTO.0b013e3181753b4b · 5.80 Impact Factor
  • Journal of Thoracic Oncology 07/2007; 2(8):S337-S338. DOI:10.1097/01.JTO.0000283149.65744.8a · 5.80 Impact Factor
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    ABSTRACT: Tumors with multidrug resistance (MDR) frequently up-regulate efflux proteins, including MDR-associated protein (MRP-1) and P-glycoprotein (Pgp). MDR represents an obstacle to successful chemotherapy treatment and is reversible in Pgp- or MRP-1-expressing cells by the inhibitor VX-710. A Phase II study was designed to evaluate VX-710 in combination with doxorubicin and vincristine in patients with sensitive, recurrent small cell lung cancer (SCLC). Eligible patients had recurrent SCLC after a response to first-line chemotherapy. Stage 1 safety evaluation was completed with planned expansion if 9 responses were confirmed in the first 35 patients. Patients were treated every 21 days until progression or intolerable adverse events (AEs). Thirty-six patients were enrolled from 1998 to 2000. Neutropenia was the major toxicity, occurring in 26 of 36 patients (72%). Neutropenia was more severe (30% vs 20% grade 4) and developed earlier (58% vs 38% in Cycle 1) among the 15 patients who were enrolled prior to an amendment that required neutropenia prophylaxis. Four patients died on study: 2 from infections likely related to therapy and 2 from cancer progression. Seven of 36 patients (19%) had partial responses; 6 patients sustained responses through 6 cycles of treatment, with 1 response lasting 3 years. Three additional patients had unconfirmed responses, and 4 patients had stable disease. The median survival was 6 months. No correlative (99m)Tc-sestamibi uptake in tumor tissue was observed with the addition of VX-710 in this study. The addition of VX-710 to doxorubicin and vincristine therapy did not significantly enhance antitumor activity or survival. Although there were durable responses, criteria were not met to proceed with Stage 2 expansion.
    Cancer 03/2007; 109(5):924-32. DOI:10.1002/cncr.22492 · 4.90 Impact Factor
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    ABSTRACT: An expanded access program (EAP) provided patient access to pemetrexed prior to its commercial availability. The current report consists of US patients in the EAP who had chemotherapy naïve pleural mesothelioma. Eligible patients had a histologic or cytologic diagnosis of malignant mesothelioma that was not amenable to curative treatment with surgery. Study treatment consisted of pemetrexed 500mg/m(2) in combination with cisplatin 75mg/m(2) once every 21 days. Vitamin B12, folic acid, and dexamethasone were administered as prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilance database for all patients enrolled in the EAP. Of 1056 patients receiving at least one dose of pemetrexed in the EAP, 728 had chemotherapy naïve pleural mesothelioma. Median age of this group was 70 years (range 23-89 years) and 84% were male. Among 615 patients, overall response rate was 20.5%, including 12 complete responses (2.0%) and 114 partial responses (18.5%). An additional 290 patients (47.2%) had stable disease. Median survival for all 728 patients was 10.8 months (95% CI=9.8, 12.3; 60.3% censorship) and 1 year survival was 45.4%. The most commonly reported SAEs in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%). In this large cohort, 67.7% of patients treated with first-line chemotherapy experienced a response or stable disease. Survival time and toxicity from this EAP were promising for this difficult-to-treat disease.
    Lung Cancer 03/2007; 55(2):187-94. DOI:10.1016/j.lungcan.2006.09.023 · 3.74 Impact Factor
  • Journal of Thoracic Oncology 01/2007; 2. DOI:10.1097/01.JTO.0000283776.57339.ce · 5.80 Impact Factor

Publication Stats

500 Citations
136.72 Total Impact Points

Institutions

  • 2012–2014
    • Mayo Clinic - Scottsdale
      Scottsdale, Arizona, United States
    • Mayo Foundation for Medical Education and Research
      • Department of Radiation Oncology
      Рочестер, Michigan, United States
  • 2006
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
    • St. James's Hospital
      Dublin, Leinster, Ireland
  • 2005–2006
    • Providence Portland Medical Center
      Portland, Oregon, United States
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States