Browsing by Author "Picus, Joel"

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    Angiokines Associated with Targeted Therapy Outcomes in Patients with Non–Clear Cell Renal Cell Carcinoma
    (AACR, 2021-06) Armstrong, Andrew J.; Nixon, Andrew B.; Carmack, Andrea; Yang, Qian; Eisen, Tim; Stadler, Walter M.; Jones, Robert J.; Garcia, Jorge A.; Vaishampayan, Ulka N.; Picus, Joel; Hawkins, Robert E.; Hainsworth, John D.; Kollmannsberger, Christian K.; Logan, Theodore F.; Puzanov, Igor; Pickering, Lisa M.; Ryan, Christopher W.; Protheroe, Andrew; George, Daniel J.; Halabi, Susan; Medicine, School of Medicine
    PURPOSE: Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC) to inform treatment selection but also to identify novel therapeutic targets. We thus sought to profile circulating angiokines in the context of a randomized treatment trial of everolimus versus sunitinib. PATIENTS AND METHODS: ASPEN (NCT01108445) was an international, randomized, open-label phase II trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC with no prior systemic therapy. Patients were randomized to everolimus or sunitinib and treated until disease progression or unacceptable toxicity. The primary endpoint was radiographic progression-free survival (PFS) defined by RECIST 1.1. Plasma angiokines were collected at baseline, cycle 3, and progression and associated with PFS and overall survival (OS). RESULTS: We enrolled 108 patients, 51 received sunitinib and 57 everolimus; of these, 99 patients had evaluable plasma for 23 angiokines. At the final data cutoff, 94 PFS and 64 mortality events had occurred. Angiokines that were independently adversely prognostic for OS were osteopontin (OPN), TIMP-1, thrombospondin-2 (TSP-2), hepatocyte growth factor (HGF), and VCAM-1, and these were also associated with poor-risk disease. Stromal derived factor 1 (SDF-1) was associated with improved survival. OPN was also significantly associated with worse PFS. No statistically significant angiokine-treatment outcome interactions were observed for sunitinib or everolimus. Angiopoeitin-2 (Ang-2), CD-73, HER-3, HGF, IL6, OPN, PIGF, PDGF-AA, PDGF-BB, SDF-1, TGF-b1-b2, TGFb-R3, TIMP-1, TSP-2, VCAM-1, VEGF, and VEGF-R1 levels increased with progression on everolimus, while CD-73, ICAM-1, IL6, OPN, PlGF, SDF-1, TGF-b2, TGFb-R3, TIMP-1, TSP-2, VEGF, VEGF-D, and VCAM-1 increased with progression on sunitinib. CONCLUSIONS: In patients with metastatic NC-RCC, we identified several poor prognosis angiokines and immunomodulatory chemokines during treatment with sunitinib or everolimus, particularly OPN.
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    Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non–Clear Cell Renal Cell Carcinoma
    (AACR, 2021-06) Armstrong, Andrew J.; Nixon, Andrew B.; Carmack, Andrea; Yang, Qian; Eisen, Tim; Stadler, Walter M.; Jones, Robert J.; Garcia, Jorge A.; Vaishampayan, Ulka N.; Picus, Joel; Hawkins, Robert E.; Hainsworth, John D.; Kollmannsberger, Christian K.; Logan, Theodore F.; Puzanov, Igor; Pickering, Lisa M.; Ryan, Christopher W.; Protheroe, Andrew; George, Daniel J.; Halabi, Susan; Medicine, School of Medicine
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    Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: A Hoosier Cancer Research Network Study
    (Springer, 2016-07) Adra, Nabil; Albany, Costantine; Brames, Mary J.; Case-Eads, Somer; Calley, Cynthia; Liu, Ziyue; Fausel, Christopher A.; Breen, Timothy; Hanna, Nasser H.; Hauke, Ralph J.; Picus, Joel; Einhorn, Lawrence H.; Department of Medicine, IU School of Medicine
    Purpose A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. Methods GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1–5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate—no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %. Results Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %). Conclusion The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin.