Ronald C DeConti

Moffitt Cancer Center, Tampa, Florida, United States

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Publications (56)389.87 Total impact

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    ABSTRACT: Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can be utilized as a neoadjuvant strategy. Data on patients with advanced locoregional BRAF V600E mutant melanoma treated with BRAF-targeted therapy at Moffitt Cancer Center were analyzed to determine response rates, subsequent resection rates after tumor downsizing, pathologic responses, and patient survival. Fifteen patients with locoregional disease treated with BRAF-targeted therapy, either BRAFi alone (vemurafenib; 11 patients) or a combination of BRAFi and an MEK inhibitor (dabrafenib plus trametinib or placebo; four patients), were identified. The median age was 50 years; the median follow-up was 25.4 months. The median BRAF-targeted therapy treatment duration was 6.0 months (range 1.2-29.4 months). Response Evaluation Criteria In Solid Tumors-based evaluation demonstrated objective response in 11 patients (73.3%). Six patients underwent resection of the remaining disease after therapy. Pathological analysis showed complete pathologic response (n=2), partial pathologic response (n=2), or no pathologic response (n=2). Four of six patients undergoing surgery have been alive for more than 2 years, including three patients currently free from active disease. No complications attributable to BRAF-targeted therapy were observed in the perioperative period. Dose reduction or discontinuation because of toxicities occurred in 10/15 patients. Neoadjuvant BRAF-targeted therapy may be effective in advanced locoregional BRAF V600E mutant melanoma patients in increasing resectability, yielding pathological responses, and achieving prolonged survival.
    No preview · Article · Jan 2016 · Melanoma research
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    ABSTRACT: BACKGROUND The purposes of this study were 1) to determine the impact of primary tumor-related factors on the prediction of the sentinel lymph node (SLN) status and 2) to identify clinical and pathologic factors associated with survival in Merkel cell carcinoma (MCC).METHODS An institutional review board–approved, retrospective review of patients with MCC treated between 1988 and 2011 at a single center was performed. Patients were categorized into 5 groups: 1) negative SLN, 2) positive SLN, 3) clinically node-negative but SLN biopsy not performed, 4) regional nodal disease without a known primary tumor, and 5) primary MCC with synchronous clinically evident regional nodal disease. Factors predictive of the SLN status were analyzed with logistic regressions, and overall survival (OS) and disease-specific survival (DSS) were analyzed with Cox models and competing risk models assuming proportional hazards, respectively.RESULTSThree hundred seventy-five patients were analyzed, and 70% were male; the median age was 75 years. The median tumor diameter was 1.5 cm (range, 0.2-12.5 cm), and the median tumor depth was 4.8 mm (range, 0.3-45.0 mm). One hundred ninety-one patients underwent SLN biopsy, and 59 (31%) were SLN-positive. Increasing primary tumor diameter and increasing tumor depth were associated with SLN positivity (P = .007 and P = .017, respectively). Age and sex were not associated with the SLN status. Immunosuppression, increasing tumor diameter, and increasing tumor depth were associated with worse OS (P = .007, P = .003, and P = .025, respectively). DSS differed significantly by group and was best for patients with a negative SLN and worst for those with primary MCC and synchronous clinically evident nodal disease (P = .018).CONCLUSION For patients with MCC, increasing primary tumor diameter and increasing tumor depth are independently predictive of a positive SLN, worse OS, and worse DSS. Tumor depth should be routinely reported when primary MCC specimens are being evaluated histopathologically. Cancer 2015. © 2015 American Cancer Society.
    No preview · Article · May 2015 · Cancer
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    ABSTRACT: Purpose: The anti-programmed death-1 (PD-1) antibody nivolumab (BMS-936558) has clinical activity in patients with metastatic melanoma. Nivolumab plus vaccine was investigated as adjuvant therapy in resected stage IIIC and IV melanoma patients. Experimental Design: HLA-A*0201 positive patients with HMB-45, NY-ESO-1, and/or MART-1 positive resected tumors received nivolumab (1mg/kg, 3mg/kg, or 10mg/kg IV) with a multi-peptide vaccine (gp100, MART-1, and NY-ESO-1 with Montanide ISA 51 VG) every 2 weeks for 12 doses followed by nivolumab maintenance every 12 weeks for 8 doses. Primary objective was safety and determination of a maximum tolerated dose (MTD). Secondary objectives included relapse free survival (RFS), overall survival (OS) and immunologic correlative studies. Results: 33 patients were enrolled. Median age was 47 years; 55% were male. Two patients had stage IIIC disease; 31 patients had stage IV disease. Median follow-up was 32.1 months. MTD was not reached. Most common related adverse events (>40%) were vaccine injection site reaction, fatigue, rash, pruritus, nausea, and arthralgias. Five related grade 3 adverse events (hypokalemia(1), rash(1), enteritis(1), and colitis(2)) were observed. 10/33 patients relapsed. Estimated median RFS was 47.1 months; median OS was not reached. Increases in CTLA-4+/CD4+, CD25+Treg/CD4+, and tetramer specific CD8+ T-cell populations were observed with treatment (P<0.05). Trends for lower baseline myeloid-derived suppressor cell and CD25+Treg/CD4+ populations were seen in non-relapsing patients; PD-L1 tumor status was not significantly associated with RFS. Conclusions: Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected melanoma, justifying further study. Copyright © 2014, American Association for Cancer Research.
    Full-text · Article · Dec 2014 · Clinical Cancer Research
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    ABSTRACT: Background Despite resection followed by adjuvant radiotherapy, high-risk cutaneous squamous cell carcinomas of the head and neck region (SCCHN) often recur. Because adjuvant concurrent chemoradiation reduces recurrence among high-risk mucosal SCCHN, we sought to understand its efficacy among high-risk cutaneous SCCHN.Methods We conducted a retrospective cohort study of patients with cutaneous SCCHN who underwent adjuvant radiation or concurrent chemoradiation. Patients must have had stage III/IV with high-risk features, including metastatic involvement of ≥2 lymph nodes, positive margins, or extracapsular invasion.ResultsThere were 61 patients: 27 (44%) received adjuvant radiation and 34 (56%) received adjuvant chemoradiation. The median recurrence-free survivals were 15.4 and 40.3 months, respectively. Adjuvant chemoradiation significantly decreased the risk of recurrence or death in a multivariable analysis: hazard ratio (HR) 0.31 (p = .01). However, a difference in overall survival was not found.Conclusion For high-risk cutaneous SCCHN, adjuvant chemoradiation was associated with a better recurrence-free survival than adjuvant radiation alone. © 2014 Wiley Periodicals, Inc. Head Neck 37: 840-845, 2015
    No preview · Article · Jun 2014 · Head & Neck
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    ABSTRACT: Background: Over the past decade, intensity-modulated radiation therapy (IMRT) has gained widespread use in the treatment of head and neck cancer. Methods: All patients with squamous cell carcinoma of the oropharynx treated with primary IMRT with or without chemotherapy over a 5-year period were reviewed. Outcomes and morbidity were analyzed and compared with previously published data. Results: In all, 170 patients were included in the analysis. The 3-year local control, locoregional control, disease-free survival, and overall survival rates were 92%, 91%, 80%, and 87%, respectively. Feeding tubes were present in 55% of patients during treatment, but remained in only 1% 2 years following treatment. Conclusions: This study confirms that IMRT yields excellent treatment outcomes for oropharyngeal carcinoma. Although acute toxicity remains a problem, late toxicity rates are low and long-term feeding tube dependence is rare compared with conventional radiation therapy.
    No preview · Article · Dec 2013 · Head & Neck
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    ABSTRACT: Squamous cell carcinoma with rhabdoid features (SCCRF) is a very rare and unusual cutaneous tumor. Here, we report an extraordinary case diagnosed by fine needle aspiration biopsy, in a 66-year-old man, status post multiple organ transplantation. The patient presented with a large ulcerating fungating mass in his forearm that had all the light microscopic and immunohistochemical features of a SCCRF. Previously six cases of SCCRF phenotype diagnosed by surgical pathology have been reported. This is the first case diagnosed cytologically. A review of the literature with emphasis on the differential diagnoses of such unusual rhabdoid-like tumors in fine-needle aspiration biopsy and the potential molecular mechanism for rhabdoid phenotype in transplant patients are discussed. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.
    No preview · Article · Feb 2013 · Diagnostic Cytopathology
  • Ronald C DeConti
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    ABSTRACT: The role of systemic chemotherapy with cytotoxic agents in squamous cell carcinoma of the skin remains uncertain. A number of agents in combination have been reported to induce high rates of remission, either alone or as a component of a multidisciplinary management plan. Fragmentary data suggest that the most benefit is achieved when chemotherapy is applied to patients with advanced local disease not easily treated with surgery either due to location (eg, on the face) or comorbidity. Concurrent chemoradiation has been recommended for the control of extensive lymph node involvement as a result of experience derived from similar studies in patients with squamous cell carcinomas of the head and neck, cervix, and anus. No standard treatment of metastatic disease has been formulated, although combinations of cisplatin with 5-fluorouracil (5-FU), doxorubicin, or bleomycin have demonstrated some degree of efficacy, achieving complete responses (CRs) in some cases. Clearly, the relative rarity of patients with high-risk, potentially fatal, squamous cell carcinoma of the skin has limited prospective efforts to define ideal management. As our awareness of the increasing numbers of such problem patients becomes clear, hopefully more efforts will be forthcoming.
    No preview · Article · Apr 2012 · Seminars in Oncology
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    Sreekanth Donepudi · Ronald C DeConti · Wolfram E Samlowski
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    ABSTRACT: Merkel cell carcinoma (MCC) is a highly aggressive skin malignancy. The growing incidence and recognition of this cancer in elderly or immunosuppressed individuals suggests that it is becoming an increasing clinical challenge. MCC recently has been demonstrated to have a probable viral pathogenesis related to a novel member of the polyomavirus (termed Merkel cell polyomavirus [MCV]). The molecular pathogenesis of viral carcinogenesis is currently being worked out in MCC. Current diagnostic and therapeutic strategies are discussed, with an eye toward the future development of molecularly targeted treatments.
    Full-text · Article · Apr 2012 · Seminars in Oncology
  • L Frank Glass · Ronald C DeConti · Vernon K Sondak

    No preview · Article · Apr 2012 · Seminars in Oncology
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    ABSTRACT: Src inhibitors sensitise melanoma cells to chemotherapy in preclinical models. The combination of dasatinib and dacarbazine was tested in a phase I trial in melanoma. Patients had ECOG performance status 0-2 and normal organ function. Dacarbazine was administered on day 1 and dasatinib on day 2 through 19 of each 21-day cycle. Both were escalated from 50 mg b.i.d. of dasatinib and 800 mg m(-2) of dacarbazine. Available pre-treatment biopsies were sequenced for BRAF, NRAS, and C-Kit mutations. Dose-limiting toxicity was reached at dasatinib 70 mg b.i.d./dacarbazine 1000 mg m(-2), and was predominantly haematological. In 29 patients receiving dasatinib 70 mg b.i.d., the objective response rate (ORR) was 13.8%, the clinical benefit rate (ORR+SD) was 72.4%, the 6-month progression-free survival (PFS) was 20.7%, and the 12-month overall survival (OS) was 34.5%. Two out of three patients who were wild type for BRAF, NRAS, and c-KIT mutations had confirmed partial responses, and one had a minor response. The recommended phase II dose is dasatinib 70 mg b.i.d with dacarbazine 800 mg m(-2). PFS and OS data for dasatinib at 70 mg b.i.d. with dacarbazine compared favourably with historical controls. Preliminary data support evaluating tumour mutation status further as a biomarker of response.
    Full-text · Article · Nov 2011 · British Journal of Cancer
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    ABSTRACT: Bortezomib, an inhibitor of the 26S proteasome and NF-κB, may have antitumor activity in adenoid cystic carcinoma (ACC). Preclinical studies have shown synergy between bortezomib and doxorubicin. Eligibility criteria included incurable ACC, any number of prior therapies but without an anthracycline, unidimensionally measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and ejection fraction within normal limits. Patients with stable disease for ≥9 months were excluded. Patients received bortezomib 1.3 mg/m(2) by intravenous (IV) push on Days 1, 4, 8, and 11, every 21 days until progression. Doxorubicin 20 mg/m(2) IV on Days 1 and 8 was added at the time of progression. Twenty-five patients were enrolled, of whom 24 were eligible; the most common distant metastatic sites were the lung (n = 22) and the liver (n = 7). There was no objective response with single-agent bortezomib; best response was stable disease in 15 (71%) of 21 evaluable patients. The median progression-free survival and overall survival were 6.4 months and 21 months, respectively. Of 10 evaluable patients who received bortezomib plus doxorubicin, 1 had a partial response, and 6 had stable disease. The most frequent toxicity with bortezomib was grade 3 sensory neuropathy (16%). With bortezomib plus doxorubicin, serious toxicities seen more than once were grade 3-4 neutropenia (n = 3) and grade 3 anorexia (n = 2). Bortezomib was well tolerated and resulted in disease stabilization in a high percentage of patients but no objective responses. The combination of bortezomib and doxorubicin was also well tolerated and may warrant further investigation in ACC.
    Full-text · Article · Aug 2011 · Cancer
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    ABSTRACT: Docosahexaenoic acid-paclitaxel (DHA-paclitaxel, Taxoprexin(®)) is made by covalently conjugating the essential fatty acid DHA to the paclitaxel molecule. Preclinical studies of DHA-paclitaxel have demonstrated increased activity relative to paclitaxel and the potential for an improved therapeutic ratio. In the present study, the efficacy and toxicity profiles of DHA-paclitaxel were compared with those of dacarbazine. In this study, 393 chemonaive patients with metastatic melanoma were randomly assigned to receive either DHA-paclitaxel at a starting dose of 900 mg/m(2) IV on day 1 every 3 weeks or dacarbazine at a starting dose of 1000 mg/m(2) IV on day 1 every 3 weeks. The primary end point of the study was the comparison of overall survival (OS). No significant difference in OS was noted between patients in the DHA-paclitaxel and dacarbazine arms. Similarly, there were no significant differences in response rate, duration of response, time to progression, and time to treatment failure between the two drugs. Safety results of the two drugs were as predicted from prior studies. Myelosuppression was more common with DHA-paclitaxel. DHA-paclitaxel was not superior to dacarbazine. We conclude that further studies with the drug on an every 3-week schedule in melanoma are not warranted.
    Preview · Article · Apr 2011 · Annals of Oncology
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    ABSTRACT: High-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon α-2b in patients with high-risk melanoma. For PK analysis, 32 patients received peginterferon α-2b 6 μg/(kg week) subcutaneously for 8 weeks (induction) then 3 μg/(kg week) for 4 weeks (maintenance). PK profiles were determined at weeks 1, 8, and 12. Exposure-response relationships between peginterferon α-2b and absolute neutrophil count (ANC) and alanine aminotransferase (ALT) level were also studied. Peginterferon α-2b was well-absorbed following SC administration, with a median T (max) of 24 h. Mean half-life estimates ranged from 43 to 51 h. The accumulation factor was 1.69 after induction therapy. PK parameters showed moderate interpatient variability. PK profiles were described by a one-compartmental model with first-order absorption and first-order elimination. Toxicity was profiled and was acceptable; observed side effects were similar to those previously described. Dose reduction produced proportional decreases in exposure and predictable effects on ANC in an Imax model; however, a PK/pharmacodynamic (PK/PD) relationship between peginterferon α-2b and ALT could not be established with high precision. Peginterferon α-2b was well-absorbed and sustained exposure to peginterferon α-2b was achieved with the doses tested. These data confirm and extend previous PK observations of peginterferon α-2b in melanoma and solid tumors. Our PK/PD model of exposure and ANC effect provides useful information for prediction of peginterferon α-2b-related hematologic toxicity.
    Full-text · Article · Mar 2011 · Cancer Chemotherapy and Pharmacology
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    ABSTRACT: Sagopilone is a novel fully synthetic epothilone with promising preclinical activity and a favourable toxicity profile in phase I testing. A phase II pharmacokinetic and efficacy trial was conducted in patients with metastatic melanoma. Patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate haematological, and organ function, with up to 2 previous chemotherapy and any previous immunotherapy regimens. Sagopilone, 16 mg m⁻², was administered intravenously over 3 h every 21 days until progression or unacceptable toxicity. Thirty-five patients were treated. Sagopilone showed multi-exponential kinetics with a mean terminal half-life of 64 h and a volume of distribution of 4361 l m⁻² indicating extensive tissue/tubulin binding. Only grade 2 or lower toxicity was observed: these included sensory neuropathy (66%), leukopenia (46%), fatigue (34%), and neutropenia (31%). The objective response rate was 11.4% (one confirmed complete response, two confirmed partial responses, and one unconfirmed partial response). Stable disease for at least 12 weeks was seen in an additional eight patients (clinical benefit rate 36.4%). Sagopilone was well tolerated with mild haematological toxicity and sensory neuropathy. Unlike other epothilones, it shows activity against melanoma even in pretreated patients. Further clinical testing is warranted.
    Full-text · Article · Oct 2010 · British Journal of Cancer
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    ABSTRACT: High-dose intravenous interleukin-2 (IL-2) therapy (14 doses/course, 2 courses/cycle) for metastatic melanoma or kidney cancer induces infrequent, although major responses. In this trial, we evaluated a new schedule (dose of 600,000 IU/kg, 8 h between doses, 5 doses/course, 4 courses at weekly intervals/cycle) of high-dose IL-2, in which we inserted more planned breaks while maintaining high cumulative dose delivery, and investigated the relationship between dendritic cells (DC) and response to treatment. Target dose delivery was attained: median IL-2 cumulative dose per patient was 11.4 and 10.8 million units/kg (cycles 1 and 2, respectively). Major responses were observed in patients with kidney cancer (n=20; 3 complete and 2 partial responses) and melanoma (n=16; 1 partial response). Adverse events appeared comparable with those typically associated with high-dose IL-2. From this data set, we introduce the hypothesis-generating observation that patients who had more favorable outcomes had high pretreatment DC-to-myeloid-derived suppressor cell (MDSC) ratios, similar to the ratio observed in healthy individuals. However, even in patients with the most favorable outcome, after treatment, there were IL-2-induced changes in the DC-to-MDSC ratio, specifically increases in MDSCs. This modified IL-2 schedule is a feasible option, with a more uniform dose delivery over the treatment cycle, a similar toxicity profile, and observed complete, durable response in patients with renal cancer. Pretreatment assessment of DC phenotypic or maturational status may be a starting point to predicting response to high-dose IL-2 cytokine immunotherapy in patients with melanoma and kidney cancer.
    No preview · Article · Oct 2010 · Journal of immunotherapy (Hagerstown, Md.: 1997)
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    Chapter: BACK MATTER
    Vernon K Sondak · Jane L Messina · Jonathan S Zager · Ronald C DeConti

    Preview · Chapter · Oct 2010
  • Ragini Kudchadkar · Ronald Deconti

    No preview · Article · Feb 2010 · Current problems in cancer
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    ABSTRACT: Imatinib mesylate (Gleevec) was evaluated as a treatment for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) based on the identification of strong c-KIT staining of these neoplasms. Eligibility included patients with measurable metastatic or unresectable MCC, c-KIT (CD117) expression and a Zubrod performance status of 0 to 2. Imatinib 400 mg daily was administered orally in 28-day cycles to 23 patients. Overall, imatinib was well tolerated with grade 1 or 2 nausea, diarrhea, and hematologic toxicity as the most frequent side effects. A partial response was seen in 1 patient (4%; 95% CI: 0%-22%). Median progression-free survival was 1 month (95% CI: 1-2 months). Median overall survival was 5 months (95% CI: 2-8 months). One patient achieved a partial response and another had prolonged disease stabilization while receiving treatment. The majority of patients progressed rapidly within 1 to 2 cycles of treatment. The observed progression-free survival and overall survival were not adequate to conclude that this agent was active in advanced MCC, and thus the planned second stage of patient accrual was not opened.
    Full-text · Article · Dec 2009 · American journal of clinical oncology
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    ABSTRACT: To investigate the potential value of postoperative concurrent chemoradiation among patients with high-risk salivary gland carcinomas. Case control study based on retrospective medical record review. A tertiary care comprehensive cancer center. A total of 24 patients, 12 with major salivary gland carcinoma who were treated with postoperative concurrent chemoradiotherapy from 1998 to 2007 (chemoradiation group), and a control group of 12 patients treated with postoperative radiation alone. Overall survival, progression-free survival, toxic effects. All but 1 patient had stage III or IV disease; close or positive surgical margins were identified in 20 patients (83%). The median radiation dose was 63 Gy. In the chemoradiation group, platinum-based regimens were used in all. Treatment was well tolerated, but toxic effects, predominantly hematologic, were increased in the chemoradiation group. To date, 8 patients have died; the median overall survival was 53 months. The overall survival in the chemoradiation group was significantly better than in the radiation-alone group: 3-year survival rates were 83% and 44%, respectively (P = .05). Locally advanced or high-grade salivary gland carcinomas follow an aggressive clinical course. Based on our limited experience, postoperative chemoradiation with a platinum-based regimen seems to be effective in selected patients and warrants further investigation.
    No preview · Article · Aug 2009 · Archives of otolaryngology--head & neck surgery
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    ABSTRACT: The novel topoisomerase I inhibitor karenitecin (KTN) shows activity against melanoma. We examined whether histone deacetylase inhibition could potentiate the DNA strand cleavage, cytotoxicity as well as the clinical toxicity, and efficacy of KTN in melanoma. Apoptosis, COMET, and xenograft experiments were carried out as described previously. A phase I/II trial of valproic acid (VPA) and KTN was conducted in patients with stage IV melanoma, with any number of prior therapies, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. VPA pretreatment potentiated KTN-induced apoptosis in multiple melanoma cell lines and in mouse A375 xenografts. VPA increased KTN-induced DNA strand breaks. In the phase I/II trial, 39 patients were entered, with 37 evaluable for toxicity and 33 evaluable for response. Somnolence was the dose-limiting toxicity. The maximum tolerated dose for VPA was 75 mg/kg/d; at maximum tolerated dose, serum VPA was approximately 200 microg/mL (1.28 mmol/L). At the dose expansion cohort, 47% (7 of 15) of patients had stable disease; median overall survival and time to progression were 32.8 and 10.2 weeks, respectively. Histone hyperacetylation was observed in peripheral blood mononuclear cells at maximum tolerated dose. VPA potentiates KTN-induced DNA strand breaks and cytotoxicity. VPA can be combined at 75 mg/kg/d for 5 days with full-dose KTN without overlapping toxicities. In metastatic poor prognosis melanoma, this combination is associated with disease stabilization in 47% of patients. Further testing of this combination appears warranted.
    Full-text · Article · May 2009 · Clinical Cancer Research

Publication Stats

3k Citations
389.87 Total Impact Points

Institutions

  • 1995-2015
    • Moffitt Cancer Center
      • Department of Biostatistics
      Tampa, Florida, United States
  • 1996-2014
    • University of South Florida
      • • Department of Oncologic Sciences
      • • Department of Surgery
      • • Moffitt Cancer Center
      Tampa, Florida, United States
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2001-2005
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2004
    • Fox Chase Cancer Center
      Filadelfia, Pennsylvania, United States
  • 1998
    • Albany Medical College
      Albany, New York, United States
  • 1993
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States