Summa Cancer Institute

Akron, Ohio, United States

Summa Cancer Institute

Akron, Ohio, United States

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Background: National Cancer Institute phase I #7336 and phase II #8327 clinical trials explored the safety and efficacy of triapine (NSC #663249) added to cisplatin radiochemotherapy in untreated patients with advancedstage cervical cancer. Triapine inhibits ribonucleotide reductase, the rate-limiting enzyme responsible for DNAbuilding deoxyribonucleotides, and thereby, enhances radiochemosensitivity by prolonging DNA repair time. Here we report 3-year efficacy endpoints of pelvic locoregional relapse rate, disease-free and overall survivals. Methods: Eligible patients with bulky IB-IIIB cervical cancer underwent three-times weekly triapine (25 or 50 mg/m2), once-weekly cisplatin (40mg/m2), and conventional daily pelvic radiation followed by brachytherapy. A cumulative incidence method estimated pelvic locoregional relapse rates. Disease-free survival was measured from radiochemotherapy start date to the date of first relapse or cancer-related death. Overall survival was measured from radiochemotherapy start date to the date of any-cause death. The Kaplan-Meier method estimated survivals. Findings: Between 2006 and 2011, 24 untreated patients with cervical cancer met criteria for reporting in this study. A median 3.4 years of follow-up time (range, 0.3-7.6 years) has been observed. All had squamous cancers and the majority had either node-positive stage IB-IIA (33%) or stage IIIB (42%) disease. The 3-year pelvic locoregional relapse rate, disease-free survival, and overall survival were 4% (95% confidence interval [CI], 0-20%), 80% (95% CI: 71-89%), and 82% (95% CI: 74%-90%), respectively. Interpretation: Triapine radiochemotherapy was safe, active, and effective in patients with untreated advancedstage cervical cancer, worthy of randomized clinical trial study. Funding: National Institutes of Health grants U01 CA62502 and P30 CA43703-17 © 2014 Kunos and Sherertz.


Kunos C.,Summa Cancer Institute | Deng W.,Roswell Park Cancer Institute | Dawson D.,Case Western Reserve University | Lea J.S.,Southwestern Medical Center | And 6 more authors.
International Journal of Gynecological Cancer | Year: 2015

Purpose: The aim of this study was to evaluate the tolerability and efficacy of poly(ADP-ribose) polymerase (PARP) inhibition by veliparib during cytotoxic topotecan administration with filgrastim or pegfilgrastim neutrophil support in women with persistent or recurrent uterine cervix cancer. Experimental Design: This phase I-II trial examined twice-daily oral veliparib (10 mg) given during once-daily intravenous topotecan (0.6 mg/m2) on days 1 to 5 of each treatment cycle. Cycles were repeated every 21 days until disease progression or until toxicity prohibited further therapy. Toxicity and objective response rate were primary endpoints. Results: Twenty-seven women were enrolled. Frequently reported grade 3 or higher treatment-related toxicities were anemia (59%), thrombocytopenia (44%), leukopenia (22%), and neutropenia (19%). There were 2 partial responses (7% [90% confidence interval, 1%-22%]). Four patients had a disease progression date more than 6 months after the start of veliparib-topotecan therapy. Patients with low immunohistochemical expression (0-1+) of PARP-1 in their primary uterine cervix cancer were more likely to have a longer progression-free interval (hazard ratio, 0.25; P = 0.02) and survival (hazard ratio, 0.12; P = 0.005) after veliparib-topotecan therapy. Conclusions: Clinical activity of a veliparib-topotecan combination was minimal in women with persistent or recurrent uterine cervix cancer. Women whose uterine cervix cancers express PARP-1 at low levels may benefit preferentially from PARP inhibitors combined with cytotoxic therapies, suggesting further study of PARP expression as an integral triage biomarker. Copyright © 2015 by IGCS and ESGO.


Kunos C.A.,Summa Cancer Institute | Sherertz T.M.,Case Western Reserve University | Mislmani M.,Case Western Reserve University | Ellis R.J.,Case Western Reserve University | And 5 more authors.
Frontiers in Oncology | Year: 2015

Background: We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers. Methods: Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m2) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1. Findings: The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m2. One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable. Interpretation: Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted. © 2015 Kunos, Sherertz, Mislmani, Ellis, Lo, Waggoner, Zanotti, Herrmann and Debernardo.


Kunos C.A.,Case Western Reserve University | Kunos C.A.,Summa Cancer Institute | Stefan T.,Case Western Reserve University | Jacobberger J.W.,Case Western Reserve University
Frontiers in Oncology | Year: 2013

Background: Up to 40% of women with ovarian cancer have short disease-free intervals due to molecular mechanisms of chemotherapy resistance. New therapeutic strategies are sought. Ovarian cancers are sensitive to radiochemotherapy. The taxane cabazitaxel (XRP6258, Jevtana) promotes tubulin assembly and stabilizes microtubules against depolymerization in cells, acting similarly in mechanism to paclitaxel. Here, sequences of cabazitaxel-radiation co-administration are tested for drug-alone cytotoxicity and optimal radiosensitization. Materials and Methods: SKOV3, OVCAR3, and TOV-112D ovarian cancer cells were administered cabazitaxel 24 h before (first), 18 h before (second), together (third), or 24 h after (fourth) a single radiation dose, and then, investigated by clonogenic assay and flow cytometric assays. Radiation dose-cell survival data were fitted by two-stage multivariate analyses of variance. High-content flow cytometry partitioned cabazitaxel effects into G2-phase versus M-phase events by DNA content, cyclin A2, and phospho-S10-histone H3 (PHH3). Paclitaxel served as a comparator. Findings: Cabazitaxel cytotoxicity and radiosensitization were dose dependent. Cabazitaxel added 24 h before radiation was the most lethal schedule. DNA content measurements by flow cytometry showed that cabazitaxel-treated cells accumulated in the radiosensitive G2/M 4C DNA complement compartment. Cytometry also showed that surviving cabazitaxel-induced cell cycle arrested cells resolve the arrest by entering 4C or by 8C DNA complement cell cycles. Interpretation: The radiosensitizing effect of cabazitaxel was schedule dependent, due to cell cycle redistribution, and best when cabazitaxel was given 24 h before radiation. Clinical trials of administering both cabazitaxel and radiation should be explored in women with chemoresistant ovarian cancer. © 2013 Kunos, Stefan and Jacobberger.


PubMed | Summa Cancer Institute and Case Western Reserve University
Type: | Journal: Frontiers in oncology | Year: 2014

National Cancer Institute phase I #7336 and phase II #8327 clinical trials explored the safety and efficacy of triapine (NSC #663249) added to cisplatin radiochemotherapy in untreated patients with advanced-stage cervical cancer. Triapine inhibits ribonucleotide reductase, the rate-limiting enzyme responsible for DNA-building deoxyribonucleotides, and thereby, enhances radiochemosensitivity by prolonging DNA repair time. Here, we report 3-year efficacy endpoints of pelvic locoregional relapse rate, disease-free, and overall survivals.Eligible patients with bulky IB-IIIB cervical cancer underwent three-times weekly triapine (25 or 50mg/m(2)), once-weekly cisplatin (40mg/m(2)), and conventional daily pelvic radiation followed by brachytherapy. A cumulative incidence method estimated pelvic locoregional relapse rates. Disease-free survival was measured from radiochemotherapy start date to the date of first relapse or cancer-related death. Overall survival was measured from radiochemotherapy start date to the date of any-cause death. The Kaplan-Meier method estimated survivals.Between 2006 and 2011, 24 untreated patients with cervical cancer met criteria for reporting in this study. A median 3.4years of follow-up time (range, 0.3-7.6years) has been observed. All had squamous cancers and the majority had either node-positive stage IB-IIA (33%) or stage IIIB (42%) disease. The 3-year pelvic locoregional relapse rate, disease-free survival, and overall survival were 4% [95% confidence interval (CI), 0-20%], 80% (95% CI: 71-89%), and 82% (95% CI: 74-90%), respectively.Triapine radiochemotherapy was safe, active, and effective in patients with untreated advanced-stage cervical cancer, worthy of randomized clinical trial study.


PubMed | Cleveland Clinic, Summa Cancer Institute and Case Western Reserve University
Type: | Journal: Frontiers in oncology | Year: 2015

We conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers.Patients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1.The maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m(2). One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable.Systemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted.


Kunos C.A.,Summa Cancer Institute | Olszewski S.,Summa Cancer Institute | Espinal E.,Summa Cancer Institute
Journal of Community and Supportive Oncology | Year: 2015

Background The Summa Cancer Institute in Akron, Ohio, sought to improve access to and the timeliness of lung cancer care by hiring an oncology-certified nurse navigator. The nurse navigator was charged with coordinating diagnostic procedures and specialty oncology consultations, and with facilitating a multidisciplinary thoracic oncology tumor board. Objective To test the hypothesis that nurse navigation would improve the timeliness of and access to diagnostic medical services among men and women with newly diagnosed lung cancer. Methods A conducted a retrospective review of 460 patients with lung cancer to evaluate access to care and the timeliness of the care received in the non-navigated and nurse-navigated cohorts. Results During December 2009-September 2013, the time between the suspicion of cancer on chest X-ray to treatment was 64 days. During October 2013-March 2014, the nurse navigator helped reduce that timespan to 45 days (P < .001). Limitations Long-term follow-up on clinical outcomes remains premature. Conclusion This finding attests to the successful implementation of nurse navigation to improve access and timeliness of lung cancer care in a community oncology practice. © 2015 Frontline Medical Communications.


Kunos C.A.,Summa Cancer Institute
Discovery Medicine | Year: 2014

Biological anticancer agents that enhance radiochemotherapeutic effect are appealing in the modern medical treatment of uterine cervix cancer. In this concise review, the focus is on three classes of biological anticancer agents. The first class is ribonucleotide reductase inhibitors. These biological anticancer agents impede deoxyribonucleotide payout and stop new synthesis of DNA molecule building blocks. By disrupting deoxyribonucleotide supply and demand economics, ribonucleotide reductase inhibitors disrupt the repair of radiation- and chemotherapy-induced DNA damage and enhance cancer cell death. Angiogenesis inhibitors represent a second class of biological anticancer agents. Angiogenesis inhibitors are conceptually thought to normalize cancer tumor vasculature and modulate vascular endothelial growth factor signals. Consequences of normalized tumor vessel permeability are better oxygen supply for radiosensitization and improved tumor fluid dynamics imparting chemosensitization. A third class, cytolytic T-cell immune modulators, edits human immune system responses to cancer cell antigens. These biological anticancer agents exploit molecular signaling involved in immune detection and in immune eradication. Completed and planned clinical trials utilizing these agents are discussed relative to the future radiochemotherapeutic management of uterine cervix cancer. © Discovery Medicine.


PubMed | Summa Cancer Institute
Type: Journal Article | Journal: The Journal of community and supportive oncology | Year: 2015

The Summa Cancer Institute in Akron, Ohio, sought to improve access to and the timeliness of lung cancer care by hiring an oncology-certified nurse navigator. The nurse navigator was charged with coordinating diagnostic procedures and specialty oncology consultations, and with facilitating a multidisciplinary thoracic oncology tumor board.To test the hypothesis that nurse navigation would improve the timeliness of and access to diagnostic medical services among men and women with newly diagnosed lung cancer.A conducted a retrospective review of 460 patients with lung cancer to evaluate access to care and the timeliness of the care received in the non-navigated and nurse-navigated cohorts.During December 2009-September 2013, the time between the suspicion of cancer on chest X-ray to treatment was 64 days. During October 2013-March 2014, the nurse navigator helped reduce that timespan to 45 days ( < .001).Long-term follow-up on clinical outcomes remains premature.This finding attests to the successful implementation of nurse navigation to improve access and timeliness of lung cancer care in a community oncology practice.


PubMed | Summa Cancer Institute
Type: Journal Article | Journal: Discovery medicine | Year: 2014

Biological anticancer agents that enhance radiochemotherapeutic effect are appealing in the modern medical treatment of uterine cervix cancer. In this concise review, the focus is on three classes of biological anticancer agents. The first class is ribonucleotide reductase inhibitors. These biological anticancer agents impede deoxyribonucleotide payout and stop new synthesis of DNA molecule building blocks. By disrupting deoxyribonucleotide supply and demand economics, ribonucleotide reductase inhibitors disrupt the repair of radiation- and chemotherapy-induced DNA damage and enhance cancer cell death. Angiogenesis inhibitors represent a second class of biological anticancer agents. Angiogenesis inhibitors are conceptually thought to normalize cancer tumor vasculature and modulate vascular endothelial growth factor signals. Consequences of normalized tumor vessel permeability are better oxygen supply for radiosensitization and improved tumor fluid dynamics imparting chemosensitization. A third class, cytolytic T-cell immune modulators, edits human immune system responses to cancer cell antigens. These biological anticancer agents exploit molecular signaling involved in immune detection and in immune eradication. Completed and planned clinical trials utilizing these agents are discussed relative to the future radiochemotherapeutic management of uterine cervix cancer.

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