Elwyn Cabebe

All Publications

• Impact of COVID-19 in patients on active melanoma therapy and with history of melanoma. BMC cancer Johnson, D. B., Atkins, M. B., Hennessy, C., Wise-Draper, T., Heilman, H., Awosika, J., Bakouny, Z., Labaki, C., Saliby, R. M., Hwang, C., Singh, S. R., Balanchivadze, N., Friese, C. R., Fecher, L. A., Yoon, J. J., Hayes-Lattin, B., Bilen, M. A., Castellano, C. A., Lyman, G. H., Tachiki, L., Shah, S. A., Glover, M. J., Flora, D. B., Wulff-Burchfield, E., Kasi, A., Abbasi, S. H., Farmakiotis, D., Viera, K., Klein, E. J., Weissman, L. B., Jani, C., Puc, M., Fahey, C. C., Reuben, D. Y., Mishra, S., Beeghly-Fadiel, A., French, B., Warner, J. L., COVID-19 and Cancer Consortium, Reid, S. A., Brown, A. J., Cheng, A., Croessmann, S., Davis, E. J., Enriquez, K. T., Gillaspie, E. A., Hausrath, D., Li, X., Slosky, D. A., Solorzano, C. C., Tucker, M. D., Vega-Luna, K., Wang, L. L., Wise-Draper, T. M., Ahmad, S. A., Grover, P., Gulati, S., Kharofa, J., Latif, T., Marcum, M., Sohal, D. P., Zamulko, O., Choueiri, T. K., Connors, J. M., Demetri, G. D., Duma, N., Freeman, D. A., Giordano, A., Morgans, A. K., Nohria, A., Saliby, R., Schmidt, A. L., Van Allen, E. M., Xu, W., Zon, R. L., Gadgeel, S. M., Tejwani, S., Boldt, A., Cohen, A. M., McWeeney, S., Nemecek, E. R., Williamson, S. P., Ravindranathan, D., Graber, J. J., Grivas, P., Hawley, J. E., Loggers, E. T., Lynch, R. C., Nakasone, E. S., Schweizer, M. T., Vinayak, S., Wagner, M. J., Yeh, A., Cabebe, E. C., Glover, M. J., Jha, A., Khaki, A. R., Schapira, L., Wu, J. T., Kloecker, G., Logan, B. B., Mandapakala, C., Rock, C. D., Arvanitis, P., Egan, P. C., Khan, H., Olszewski, A. J., Vieira, K., Weissmann, L. B., Bhatt, P. S., Mariano, M. G., Thomson, C. C., Carducci, T. M., Goldsmith, K. J., Van Loon, S., Alexander, M., Matar, S., Mushtaq, S., Stockerl-Goldstein, K. E., Butt, O., Fiala, M. A., Henderson, J. P., Monahan, R. S., Zhou, A. Y., Lammers, P. E., Revankar, S. G., Del Prete, S. A., Bar, M. H., Gulati, A. P., Lo, K. M., Rose, S. J., Stratton, J., Weinstein, P. L., Gupta, S., Pennell, N. A., Ahluwalia, M. S., Dawsey, S. J., Lemmon, C. A., Nizam, A., Sharifi, N., Hoppenot, C., Li, A., Halabi, S., Dzimitrowicz, H., Zhang, T., Goyal, S., Huynh-Le, M., Yu, P. P., Clement, J. M., Daher, A., Dailey, M. E., Elias, R., Jayaraj, A., Hsu, E., Menendez, A. G., Serrano, O. K., Accordino, M. K., Bhutani, D., Hershman, D., Ingham, M. A., Schwartz, G. K., Bernicker, E. H., Deeken, J. F., Shafer, D., Ruiz-Garcia, E., Ramirez, A., Vilar-Compte, D., Lewis, M. A., Rhodes, T. D., Gill, D. M., Low, C. A., Mashru, S. H., Mansoor, A., Lewis, G. C., Smith, S. J., Zaren, H. A., Nagaraj, G., Akhtari, M., Castillo, D. R., Lau, E., Reeves, M. E., Berg, S., Knox, N., O'Connor, T. E., Durbin, E. B., Kulkarni, A. A., Nelson, H. H., Sachs, Z., Rosovsky, R. P., Reynolds, K. L., Bardia, A., Boland, G., Gainor, J. F., Zubiri, L., Halfdanarson, T. R., Bekaii-Saab, T. S., Desai, A., Riaz, I. B., Shah, S., Smith, K. E., Williams, C., Bouganim, N., Elkrief, A., Panasci, J., Vinh, D. C., Riely, G. J., Belenkaya, R., Philip, J., Faller, B., McKay, R. R., Ajmera, A., Brouha, S. S., Choi, S., Hsiao, A., Kligerman, S., Nonato, T. K., Blau, E. G., Jhawar, S. R., Addison, D., Chen, J. L., Gatti-Mays, M. E., Karivedu, V., Karivedu, V., Palmer, J. D., Stover, D. G., Wall, S., Williams, N. O., Joshi, M., Polimera, H. V., Pomerantz, L. D., Rovito, M. A., Griffiths, E. A., Advani, P. G., Puzanov, I., Jabbour, S. K., Misdary, C. F., Shah, M. R., Batist, G., Cook, E., Dutra, M. S., Ferrario, C., Miller, W. H., Bashir, B., McNair, C., Mahmood, S. Z., Mico, V., Rivera, A. V., Edwin, N. C., Smits, M., Doroshow, D. B., Galsky, M. D., Wotman, M., Fazio, A., Fu, J. C., Huber, K. E., Sueyoshi, M. H., Koshkin, V. S., Borno, H. T., Kwon, D. H., Small, E. J., Zhang, S., Rubinstein, S. M., Wood, W. A., Andermann, T. M., Jensen, C., Bowles, D. W., Geiger, C. L., Feldman, L. E., Hoskins, K. F., Gantt, G. J., Liu, L. C., Khan, M., Nguyen, R. H., Pasquinelli, M., Schwartz, C., Venepalli, N. K., Mavromatis, B. H., Bijjula, R. R., Zaman, Q. U., Aboulafiam, D. M., Schroeder, B. A., Topaloglu, U., Alimohamed, S. I., Moore, J. K., Peddi, P., Rosen, L. R., McCollough, B. B., Hafez, N., Herbst, R., LoRusso, P., Lustberg, M. B., Masters, T., Stratton, C. 2023; 23 (1): 265

  Abstract

  INTRODUCTION: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy.METHODS: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors.RESULTS: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35).CONCLUSIONS: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors.

  View details for DOI 10.1186/s12885-023-10708-6

  View details for PubMedID 36949413

• Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19. JAMA oncology Bakouny, Z., Labaki, C., Grover, P., Awosika, J., Gulati, S., Hsu, C. Y., Alimohamed, S. I., Bashir, B., Berg, S., Bilen, M. A., Bowles, D., Castellano, C., Desai, A., Elkrief, A., Eton, O. E., Fecher, L. A., Flora, D., Galsky, M. D., Gatti-Mays, M. E., Gesenhues, A., Glover, M. J., Gopalakrishnan, D., Gupta, S., Halfdanarson, T. R., Hayes-Lattin, B., Hendawi, M., Hsu, E., Hwang, C., Jandarov, R., Jani, C., Johnson, D. B., Joshi, M., Khan, H., Khan, S. A., Knox, N., Koshkin, V. S., Kulkarni, A. A., Kwon, D. H., Matar, S., McKay, R. R., Mishra, S., Moria, F. A., Nizam, A., Nock, N. L., Nonato, T. K., Panasci, J., Pomerantz, L., Portuguese, A. J., Provenzano, D., Puc, M., Rao, Y. J., Rhodes, T. D., Riely, G. J., Ripp, J. J., Rivera, A. V., Ruiz-Garcia, E., Schmidt, A. L., Schoenfeld, A. J., Schwartz, G. K., Shah, S. A., Shaya, J., Subbiah, S., Tachiki, L. M., Tucker, M. D., Valdez-Reyes, M., Weissmann, L. B., Wotman, M. T., Wulff-Burchfield, E. M., Xie, Z., Yang, Y. J., Thompson, M. A., Shah, D. P., Warner, J. L., Shyr, Y., Choueiri, T. K., Wise-Draper, T. M. 2022

  Abstract

  Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.This registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.ClinicalTrials.gov Identifier: NCT04354701.

  View details for DOI 10.1001/jamaoncol.2022.5357

  View details for PubMedID 36326731

• Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States. JAMA network open Hawley, J. E., Sun, T., Chism, D. D., Duma, N., Fu, J. C., Gatson, N. T., Mishra, S., Nguyen, R. H., Reid, S. A., Serrano, O. K., Singh, S. R., Venepalli, N. K., Bakouny, Z., Bashir, B., Bilen, M. A., Caimi, P. F., Choueiri, T. K., Dawsey, S. J., Fecher, L. A., Flora, D. B., Friese, C. R., Glover, M. J., Gonzalez, C. J., Goyal, S., Halfdanarson, T. R., Hershman, D. L., Khan, H., Labaki, C., Lewis, M. A., McKay, R. R., Messing, I., Pennell, N. A., Puc, M., Ravindranathan, D., Rhodes, T. D., Rivera, A. V., Roller, J., Schwartz, G. K., Shah, S. A., Shaya, J. A., Streckfuss, M., Thompson, M. A., Wulff-Burchfield, E. M., Xie, Z., Yu, P. P., Warner, J. L., Shah, D. P., French, B., Hwang, C., COVID-19 and Cancer Consortium (CCC19), Halmos, B., Verma, A. K., Gartrell, B. A., Goel, S., Ohri, N., Sica, R. A., Thakkar, A., Stockerl-Goldstein, K. E., Butt, O., Campian, J. L., Fiala, M. A., Henderson, J. P., Monahan, R., Zhou, A. Y., Thompson, M. A., Bohachek, P., Mundt, D., Streckfuss, M., Tadesse, E., Lammers, P. E., Panagiotou, O. A., Egan, P. C., Farmakiotis, D., Khan, H., Olszewski, A. J., Loaiza-Bonilla, A., Del Prete, S. A., Bar, M. H., Gulati, A. P., Steve Lo, K. M., Rose, S. J., Stratton, J., Weinstein, P. L., Caimi, P. F., Barnholtz-Sloan, J. S., Garcia, J. A., Nakayama, J. M., Gupta, S., Pennell, N. A., Ahluwalia, M. S., Dawsey, S. J., Lemmon, C. A., Nizam, A., Hoppenot, C., Li, A., Choueiri, T. K., Bakouny, Z., Bouchard, G., Busser, F. J., Connors, J. M., Curran, C. R., Demetri, G. D., Giordano, A., Kelleher, K., Nohria, A., Schmidt, A., Shaw, G., Van Allen, E., Vitale, P., Xu, V., Zon, R. L., Zhang, T., Halabi, S., Leighton, J. C., Lyman, G. H., Graber, J. J., Grivas, P., Khaki, A. R., Loggers, E. T., Lynch, R. C., Nakasone, E. S., Schweizer, M. T., Tachiki, L., Vinayak, S., Wagner, M. J., Yeh, A., Gatson, N. T., Goyal, S., Huynh-Le, M., Rosenstein, L. J., Yu, P. P., Clement, J. M., Daher, A., Dailey, M., Elias, R., Jayaraj, A., Hsu, E., Menendez, A. G., Rathmann, J., Serrano, O., Hwang, C., Gadgeel, S. M., Singh, S. R., Hawley, J. E., Hershman, D., Accordino, M. K., Bhutani, D., Schwartz, G. K., Reuben, D. Y., Alexander, M., Mushtaq, S., Bernicker, E. H., Deeken, J., Shafer, D., Lewis, M. A., Rhodes, T. D., Gill, D. M., Low, C. A., Mashru, S. H., Mansoor, A., Zaren, H. A., Smith, S. J., Nagaraj, G., Akhtari, M., Lau, E., Reeves, M. E., Berg, S., Elms, D., Morgans, A. K., Wehbe, F. H., Altman, J., Gurley, M., Mulcahy, M. F., Durbin, E. B., Kulkarni, A. A., Nelson, H. H., Sachs, Z., Shah, S., Rosovsky, R. P., Reynolds, K., Bardia, A., Boland, G., Gainor, J., Zubiri, L., Halfdanarson, T. R., Bekaii-Saab, T., Desai, A., Xie, Z., Mesa, R. A., Bonnen, M., Mahadevan, D., Ramirez, A. G., Salazar, M., Shah, D. P., Shah, P. K., Faller, B., McKay, R. R., Ajmera, A., Brouha, S. S., Cabal, A., Hsiao, A., Kligerman, S., Shaya, J. A., Weissmann, L. B., Jani, C., Thomson, C. C., Knoble, J., Glace, M. G., Rink, C., Stauffer, K., Zacks, R., Blau, S., Joshi, M., Menon, H., Rovito, M. A., Griffiths, E. A., Elshoury, A., Jabbour, S. K., Misdary, C. F., Shah, M. R., Bashir, B., McNair, C., Mahmood, S. Z., Mico, V., Rivera, A. V., Flora, D. B., Logan, B. B., Kloecker, G., Mandapakala, C., Shah, S. A., Cabebe, E. C., Glover, M. J., Jha, A., Schapira, L., Wu, J. T., Subbiah, S., Lopes, G. d., Revankar, S. G., Stover, D. G., Addison, D., Chen, J. L., Gatti-Mays, M. E., Jhawar, S. R., Karivedu, V., Lustberg, M. B., Palmer, J. D., Wall, S., Williams, N., Wulff-Burchfield, E., Kasi, A., Edwin, N., Smits, M., Chism, D. D., Owenby, S., Doroshow, D. B., Galsky, M. D., Wotman, M., Zhu, H., Fu, J. C., Fazio, A., Sueyoshi, M. H., Huber, K. E., Riess, J., Patel, K. G., Rubinstein, S. M., Wood, W. A., Jensen, C., Kumar, V., Wise-Draper, T. M., Ahmad, S. A., Grover, P., Gulati, S., Kharofa, J., Latif, T., Marcum, M., Park, C., Shaikh, H. G., Bowles, D. W., Geiger, C. L., Markham, M., Bishnoi, R., Russ, A. D., Shah, C., Acoba, J. D., Rho, Y. S., Feldman, L. E., Hoskins, K. F., Gantt, G. J., Liu, L. C., Khan, M., Nguyen, R. H., Pasquinelli, M., Schwartz, C., Venepalli, N. K., Vikas, P., Friese, C. R., Fecher, L. A., Mavromatis, B. H., Bijjula, R. R., Zaman, Q. U., Warner, J. L., Cheng, A., Davis, E. J., Duda, S. N., Enriquez, K. T., French, B., Gillaspie, E. A., Hennessy, C., Hausrath, D., Hsu, C., Johnson, D. B., Li, X., Mishra, S., Reid, S. A., Rini, B. I., Slosky, D. A., Shyr, Y., Solorzano, C. C., Sun, T., Tucker, M. D., Vega-Luna, K., Wang, L. L., Kennecke, H. F., Aboulafia, D. M., Schroeder, B. A., Puc, M., Carducci, T. M., Goldsmith, K. J., Van Loon, S., Topaloglu, U., Alimohamed, S. I., Rice, R. L., Cabalona, W. D., Pilar, C., Peddi, P., Rosen, L. R., McCollough, B. B., Bilen, M. A., Ravindranathan, D., Hafez, N., Herbst, R., LoRusso, P., Masters, T., Stratton, C. 1800; 5 (1): e2142046

  Abstract

  Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography.Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer.Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States.Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index.Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time.Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58).Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients.

  View details for DOI 10.1001/jamanetworkopen.2021.42046

  View details for PubMedID 34982158

• Durvalumab for Stage III EGFR-Mutated Non-Small Cell Lung Cancer After Definitive Chemoradiotherapy. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer Aredo, J. V., Mambetsariev, I. n., Hellyer, J. A., Amini, A. n., Neal, J. W., Padda, S. K., McCoach, C. E., Riess, J. W., Cabebe, E. C., Naidoo, J. n., Abuali, T. n., Salgia, R. n., Loo, B. W., Diehn, M. n., Han, S. S., Wakelee, H. A. 2021

  Abstract

  In 2018, durvalumab was FDA approved as consolidation immunotherapy for patients with stage III non-small cell lung cancer (NSCLC) after definitive chemoradiotherapy (CRT). Whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown.We conducted a multi-institutional retrospective analysis of patients with unresectable stage III EGFR-mutated NSCLC who completed concurrent CRT. Kaplan-Meier analyses evaluated progression-free survival (PFS) between patients who completed CRT with or without durvalumab.Among 37 patients, 13 initiated durvalumab a median of 20 days after CRT completion. Two patients completed 12 months of treatment, with five patients discontinuing durvalumab due to progression and five due to immune-related adverse events (irAEs). Of 24 patients who completed CRT without durvalumab, 16 completed CRT alone and 8 completed CRT with induction or consolidation EGFR tyrosine kinase inhibitors (TKI). Median PFS was 10.3 months in patients who received CRT and durvalumab versus 6.9 months with CRT alone (log-rank P=0.993). CRT and EGFR TKI was associated with a significantly longer median PFS (26.1 months) compared to CRT and durvalumab or CRT alone (log-rank P=0.023). Six patients treated with durvalumab initiated EGFR TKIs after recurrence, with one developing grade 4 pneumonitis on osimertinib.In this study, patients with EGFR-mutated NSCLC did not benefit with consolidation durvalumab and experienced a high frequency of irAEs. Patients who initiate osimertinib after durvalumab may be susceptible to incident irAEs. Consolidation durvalumab should be approached with caution in this setting and concurrent CRT with induction and/or consolidation EGFR TKIs further investigated as definitive treatment.

  View details for DOI 10.1016/j.jtho.2021.01.1628

  View details for PubMedID 33588109

• A phase I trial of vandetanib combined with capecitabine, oxaliplatin and bevacizumab for the first-line treatment of metastatic colorectal cancer INVESTIGATIONAL NEW DRUGS Cabebe, E. C., Fisher, G. A., Sikic, B. I. 2012; 30 (3): 1082-1087

  Abstract

  Vandetanib is a tyrosine kinase inhibitor of both the vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) receptors. The primary objectives of this study were to determine the maximum tolerated dose of vandetanib with capecitabine and oxaliplatin, without and with bevacizumab, for the first line treatment of metastatic colorectal cancer (mCRC), and to define the dose limiting toxicities.Three cohorts of patients were studied, with capecitabine at 1,000 mg/m(2) twice daily p.o. on days 1-14 of a 3 week cycle, with oxaliplatin i.v. at 130 mg/m(2) on day 1. Vandetanib dosing was 100 mg/day in cohort 1 and 300 mg/day in cohorts 2 and 3. Bevacizumab was added in cohort 3 at 7.5 mg/kg i.v. on day 1 every 3 weeks.Thirteen patients were enrolled and received from one to eight cycles per patient. Grade 4 dermatitis developed in one patient in the first cohort, and the cohort was expanded to six patients with no further dose limiting toxicities (DLT). The second cohort of 3 patients was well tolerated. The third cohort resulted in grade 3 diarrhea, requiring several days of hospitalization and i.v. hydration, in 3 of the 4 patients. Given the severity and duration of diarrhea, each of these was considered a DLT, and therefore cohort 3 was considered to be above the maximum tolerated dose. Six of the 13 patients achieved a partial or complete remission (46%). The time to progression ranged from 2 to 14 months.Vandetanib at doses of 100 mg and 300 mg daily in combination with capecitabine and oxaliplatin was well tolerated. However, the addition of bevacizumab resulted in severe diarrhea in three out of four patients. Bevacizumab was not well tolerated with vandetanib and XELOX in combination.

  View details for DOI 10.1007/s10637-011-9656-y

  View details for Web of Science ID 000303878700023

  View details for PubMedID 21404105

• Clinical trials of VEGF receptor tyrosine kinase inhibitors in pancreatic cancer EXPERT OPINION ON INVESTIGATIONAL DRUGS Cabebe, E., Fisher, G. A. 2007; 16 (4): 467-476

  Abstract

  Pancreatic cancer is the fourth leading cause of cancer-related deaths in Western countries and is among the deadliest diseases in humans. At present, gemcitabine is the standard chemotherapy for advanced pancreatic cancer, although (despite its use) prognosis continues to be dismal with a median survival of < 6 months. While targeting tumor vasculature has provided improved outcomes in colon, lung, breast and renal cell cancers, trials of angiogenesis inhibitors have lagged behind in pancreatic cancer. This review provides the rationale for exploring antiangiogenic therapies in the treatment of pancreatic cancer as well as summarizes present clinical development of VEGF receptor tyrosine kinase inhibitors and their application to pancreatic cancer.

  View details for DOI 10.1517/13543784.16.4.467

  View details for Web of Science ID 000245307500007

  View details for PubMedID 17371195

• Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Current treatment options in oncology Cabebe, E., Wakelee, H. 2007; 8 (1): 15-27

  Abstract

  OPINION STATEMENT: Successful inhibition of angiogenesis with the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has improved the efficacy seen with standard cytotoxic therapy in NSCLC. The addition of bevacizumab to first-line chemotherapy improved response rate and progression free survival and added 2 months to median overall survival for those patients with advanced stage NSCLC on the treatment arm of E4599. Bevacizumab is now a standard agent to add to frontline carboplatin and paclitaxel for patients with newly diagnosed NSCLC who meet the eligibility criteria from the landmark E4599 trial. Unfortunately about half of all patients are not eligible either because they have squamous histology, brain metastases, or are on anti-coagulation. Ongoing trials are further exploring the safety of bevacizumab in these patient populations, as well as in combination with other cytotoxic regimens. Exploration of other applications of bevacizumab in the second-line and adjuvant setting are ongoing as well. The largest class of drugs that block angiogenesis are the multi-targeted tyrosine kinase inhibitors (TKIs) that target the VEGF receptor (VEGFR). These drugs are still in development, and though two are now on the market for treating other malignancies, their role in NSCLC is under investigation. These agents have the advantages of hitting multiple targets, convenient oral administration, and potential for lower cost. Their lack of target specificity leads to unexpected toxicity, but also promising efficacy. For example, the overall objective response rate of 9.5% with single agent sunitinib compares similarly to that of pemetrexed or docetaxel in previously treated NSCLC patients, but toxicity, notably fatigue, lead to discontinuation in 38% of patients. Hypertension, hemorrhage and cavitation are common toxicities amongst this class of agents. Rash, fatigue, myalgia, and hand-foot syndrome are more specifically seen with TKIs. These compounds may also be synergistic or additive with traditional cytotoxic chemotherapy drugs and other novel compounds. In early trials sorafenib as a single agent has shown no clinical response in previously treated NSCLC patients, whereas clinical benefit in combination with erlotinib or chemotherapy has been seen in early studies. Vandetanib has demonstrated objective responses as a single agent and in combination with chemotherapy in previously treated NSCLC patients. A phase I trial of AZD2171 with carboplatin and paclitaxel in newly diagnosed advanced stage NSCLC also demonstrated promising results with 6 of 15 patients achieving partial responses. NSCLC specific trials are also underway, or in development for pazopanib, axitinib, AMG 706, XL647, enzastaurin, and other TKIs. Other anti-angiogenesis agents with different mechanisms of action include thalidomide and its derivatives, monoclonal antibodies to the VEGFRs, and VEGF Trap, a chimeric molecule which combines extracellular portions of VEGFR1 and VEGFR2 with the Fc portion of immunoglobulin G1 to form a molecule that binds and "traps" VEGF. Despite modest improvements, prognosis continues to be poor for patients with advanced NSCLC. Bevacizumab is a first step into the world of angiogenesis inhibitors for NSCLC and though it only offers a modest survival benefit in a limited patient population, it paves the way for the development of the next generation of anti-angiogenesis inhibitors. We can hope that further improvements in survival will follow.

  View details for PubMedID 17634832

• Sunitinib: A newly approved small-molecule inhibitor of angiogenesis DRUGS OF TODAY Cabebe, E., Wakelee, H. 2006; 42 (6): 387-398

  Abstract

  The advent of targeted therapies has allowed treatment to be directed at signaling pathways integral to tumor growth and survival. Sunitinib (SU11248, sunitinib malate; Pfizer Inc., New York, NY, USA) is a novel oral small-molecule multitargeted receptor tyrosine kinase inhibitor that has demonstrated direct antitumor activity and antiangiogenic action. It targets the vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), stem-cell factor receptor and Fms-like tyrosine kinase receptor 3 receptor tyrosine-kinases. In January 2006, sunitinib malate was granted approval by the U.S. Food and Drug Administration for the treatment of gastrointestinal stromal tumor after disease progression on, or intolerance to, imatinib mesylate, as well as for the treatment of metastatic renal cell cancer. This review will discuss the development of sunitinib, particularly in acute myeloid leukemia, imatinib-resistant gastrointestinal stromal tumors and renal cell cancer. The review will also discuss ongoing trials with sunitinib in other malignancies such as neuroendocrine tumors and breast cancer, as well as its potential future development in combination therapy with other agents and in other malignancies.

  View details for DOI 10.1358/dot.2006.42.6.985633

  View details for PubMedID 16845442

• Intensity-modulated radiation therapy for the spine at the University of California, Irvine. Medical dosimetry Kuo, J. V., Cabebe, E., Al-Ghazi, M., Yakoob, I., Ramsinghani, N. S., Sanford, R. 2002; 27 (2): 137-145

  Abstract

  Radiation treatment of malignant diseases of the spine poses unique challenges to the radiation oncology treatment team. Intensity-modulated radiation therapy (IMRT) offers the capability of delivering high doses to targets near the spine while respecting spinal cord tolerance. At the University of California, Irvine, 8 patients received a total of 10 courses to the spine for a variety of primary and metastatic malignant conditions. This paper discusses anatomical considerations, spinal cord radiation myelopathy, and treatment planning issues as it relates to the treatment of spinal cord lesions. Between October 1997 and August 2001, a total of 8 patients received 10 courses of IMRT for primary or metastatic disease of the spine. Cancers treated included metastatic lung, renal, adrenocortical cancers, and primary sarcomas and giant cell tumor. Five cases had 6 courses given for re-irradiation of symptomatic disease and 3 cases had 4 courses of IMRT as primary management of their spinal lesions. Although 3 courses were given postoperatively, these were for grossly residual disease. For the re-irradiation patients, the mean follow-up interval was 4 months. The local control was estimated at 14%. Of the patients treated with primary intent, the mean follow-up was 9 months and the local control rate 75%. No patients developed spinal cord complications.

  View details for PubMedID 12074465