D Raghavan

Carolinas HealthCare System, Charlotte, North Carolina, United States

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Publications (236)1534.17 Total impact

  • Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 07/2014;
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    ABSTRACT: Neoadjuvant cisplatin-based combination chemotherapy provides a 5% increase in cure rate, an increase in median survival of about 3 years, and statistically significant and clinically relevant increments in overall survival for patients with invasive bladder cancer. Despite compelling level 1 data, it has become quite clear that facts that are similar to those that changed the paradigm of treatment of breast cancer in the 1970s have not had a similar influence on patterns of practice in bladder cancer care. Instead of using this proven approach, cystectomy alone or surgery followed by adjuvant chemotherapy is often used as a functional alternative for patients with deeply invasive and/or node-metastatic disease discovered at radical cystectomy. However, there is no well-powered level 1 evidence to support routine adjuvant chemotherapy for invasive bladder cancer, and some randomized trials have shown inferior outcomes. There is a clear need for a well designed, randomized trial that tests the utility of adjuvant chemotherapy for invasive bladder cancer, but until that has been completed, neoadjuvant chemotherapy followed by definitive local treatment should be the standard of care for invasive bladder cancer.
    Annals of Oncology 02/2014; · 7.38 Impact Factor
  • Derek Raghavan
    Seminars in Oncology 12/2013; 40(6):659-661. · 4.33 Impact Factor
  • Journal of Clinical Oncology 10/2013; · 18.04 Impact Factor
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    ABSTRACT: Many challenges to clinical trial accrual exist, resulting in studies with inadequate enrollment and potentially delaying answers to important scientific and clinical questions. The National Cancer Institute (NCI) and the ASCO (ASCO) cosponsored the Cancer Trial Accrual Symposium: Science and Solutions on April 29-30, 2010 to examine the state of accrual science related to patient/community, physician/provider, and site/organizational influences, and identify new interventions to facilitate clinical trial enrollment. The symposium featured breakout sessions, plenary sessions, and a poster session including 100 abstracts. Among the 358 attendees were clinical investigators, researchers of accrual strategies, research administrators, nurses, research coordinators, patient advocates, and educators. A bibliography of the accrual literature in these three major areas was provided to participants in advance of the meeting. After the symposium, the literature in these areas was revisited to determine if the symposium recommendations remained relevant within the context of the current literature. Few rigorously conducted studies have tested interventions to address challenges to clinical trials accrual. Attendees developed recommendations for improving accrual and identified priority areas for future accrual research at the patient/community, physician/provider, and site/organizational levels. Current literature continues to support the symposium recommendations. A combination of approaches addressing both the multifactorial nature of accrual challenges and the characteristics of the target population may be needed to improve accrual to cancer clinical trials. Recommendations for best practices and for future research developed from the symposium are provided.
    Journal of Oncology Practice 10/2013;
  • Derek Raghavan
    European journal of cancer (Oxford, England: 1990) 07/2013; · 4.12 Impact Factor
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    ABSTRACT: Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence. Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization. A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy groufp and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events. Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).
    New England Journal of Medicine 04/2013; 368(14):1314-25. · 51.66 Impact Factor
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    ABSTRACT: Purpose Enzastaurin is an oral serine/threonine kinase inhibitor that inhibits the beta isoform of protein kinase C and which may have therapeutic activity in prostate cancer. We explored the efficacy of docetaxel/prednisone with or without enzastaurin in patients with castration-resistant metastatic prostate cancer. Methods A nonrandomized safety cohort consisting of 14 patients was followed by a double-blind randomized Phase II trial. Patients received standard doses of docetaxel (75 mg/m(2)) with prednisone 10 mg daily with or without 500 mg/day of enzastaurin. Results There was no difference in the objective response rate between the enzastaurin and placebo arms (placebo: 7 [15.2 %]; enzastaurin: 6 [15.0 %]; P = 1.00). The median PFS was 229 days for patients in the enzastaurin arm versus 213 days for the placebo arm (P = 0.524). The 1-year overall survival rates were almost identical, with 76.7 % and 75.1 % in the enzastaurin and placebo arms, respectively. Therapy was well tolerated although the combination of enzastaurin and docetaxel was more myelosuppressive than with docetaxel alone. Conclusions The clinical activity of docetaxel/prednisone plus enzastaurin cannot be distinguished from docetaxel/prednisone alone, given the limitations of a randomized Phase II design. Although the toxicity profile was favorable for the enzastaurin-containing regimen, there is no compelling rationale to move this combination forward for the treatment of castration-resistant metastatic prostate cancer.
    Investigational New Drugs 02/2013; · 3.50 Impact Factor
  • Derek Raghavan
    The Oncologist 01/2013; 18(8):895-6. · 4.10 Impact Factor
  • Derek Raghavan
    Mayo Clinic Proceedings 01/2013; 88(1):1-3. · 5.79 Impact Factor
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    ABSTRACT: Small cell bladder cancer (SCBC) is a rare and aggressive form of bladder cancer. It exhibits similar biological behavior to small cell lung carcinoma. Untreated, it is associated with a very poor prognosis. Appropriate oncologic surgery remains the mainstay of treatment of this disease but is not curative alone in the majority of the cases. Adding systemic therapy to the treatment regimen has been shown to improve survival. The most common chemotherapy regimens used in published series include a platinum complex plus etoposide, although doxorubicin-based regimens and standard urothelial cancer regimens also have been associated with response. Despite robust chemotherapy responses, metastatic disease is associated with relapse and a median overall survival of 18 months or less. Better understanding of the molecular alterations driving SCBC may facilitate the development of new therapeutic strategies and improved outcomes.
    Seminars in Oncology 10/2012; 39(5):615-8. · 4.33 Impact Factor
  • Derek Raghavan
    Seminars in Oncology 10/2012; 39(5):523. · 4.33 Impact Factor
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    ABSTRACT: Throughout the world there are problems recruiting ethnic minority patients into cancer clinical trials. A major barrier to trial entry may be distrust of research and the medical system. This may be compounded by the regulatory framework governing research with an emphasis on written consent, closed questions and consent documentation, as well as fiscal issues. The Leicester UK experience is that trial accrual is better if British South Asian patients are approached by a senior doctor rather than someone of perceived lesser hierarchical status and a greater partnership between the hospital and General Practitioner may increase trial participation of this particular ethnic minority. In Los Angeles, USA, trial recruitment was improved by a greater utilisation of Hispanic staff and a Spanish language-based education programme. Involvement of community leaders is essential. While adhering to national, legal and ethnical standards, information sheets and consent, it helps if forms can be tailored towards the local ethnic minority population. Written translations are often of limited value in the recruitment of patients with no or limited knowledge of English. In some cultural settings, tape-recorded verbal consent (following approval presentations) may be an acceptable substitute for written consent, and appropriate legislative changes should be considered to facilitate this option. Approaches should be tailored to specific minority populations, taking consideration of their unique characteristics and with input from their community leadership.
    British Journal of Cancer 09/2012; 107(7):1017-21. · 5.08 Impact Factor
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    ABSTRACT: This correspondence is in response to the article: Abratt RP. The fast neutron therapy programme for patients in South Africa should come to an end. S Afr Med J 2012;102(2):58. Other correspondence in this series: Neutron radiotherapy: a different perspective. S Afr Med J 2012;102(5):269; Neutron radiotherapy should continue. S Afr Med J 2012;102(5):269-270; Neutron radiotherapy, Abratt reply. S Afr Med J 2012;102(5):270-217; Neutron radiotherapy: Society comments. S Afr Med J 2012;102(5):271.
    South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 05/2012; 102(5):271. · 1.70 Impact Factor
  • Journal of Clinical Oncology 04/2012; 30(14):1715-24. · 18.04 Impact Factor
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    ABSTRACT: The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival. We conducted a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG) with GC in patients with locally advanced or metastatic urothelial carcinoma. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate, and toxicity. From 2001 to 2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and 314 patients were assigned to GC. After a median follow-up of 4.6 years, the median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR], 0.85; P = .075). OS in the subgroup of all eligible patients was significantly longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P = .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both treatments were well tolerated, with more thrombocytopenia and bleeding on GC than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on PCG than GC (13.2% v 4.3%, respectively; P < .001). The addition of paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit that did not reach statistical significance. Novel approaches will be required to obtain major improvements in survival of incurable urothelial cancer.
    Journal of Clinical Oncology 02/2012; 30(10):1107-13. · 18.04 Impact Factor
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    Siran M Koroukian, Paul M Bakaki, Derek Raghavan
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    ABSTRACT: A study was undertaken to compare survival and 5-year mortality by Medicaid status in adults diagnosed with 8 select cancers. Linking records from the Ohio Cancer Incidence Surveillance System (OCISS) with Ohio Medicaid enrollment data, the authors identified Medicaid and non-Medicaid patients aged 15 to 54 years and diagnosed with the following incident cancers in the years 1996-2002: cancer of the testis; Hodgkin and non-Hodgkin lymphoma; early stage melanoma, colon, lung, and bladder cancer; and pediatric malignancies (n = 12,703). Medicaid beneficiaries were placed in the pre-diagnosis group if they were enrolled in Medicaid at least 3 months before cancer diagnosis, and in the peri/post-diagnosis group if they enrolled in Medicaid upon or after being diagnosed with cancer. The authors also linked the OCISS with death certificates and data from the US Census. By using Cox and logistic regression analysis, they examined the association between Medicaid status and survival and 5-year mortality, respectively, after adjusting for patient covariates. Nearly 11% of the study population were Medicaid beneficiaries. Of those, 45% were classified in the peri/post-diagnosis group. Consistent with higher mortality, findings from the Cox regression model indicated that compared with non-Medicaid, patients in the Medicaid pre-diagnosis and peri/post-diagnosis groups experienced unfavorable survival outcomes (adjusted hazard ratio [AHR], 1.52; 95% confidence interval [CI], 1.27-1.82 and AHR, 2.01; 95% CI, 1.70-2.38, respectively). Medicaid status was associated with unfavorable survival, even after adjusting for confounders. The findings reflect the vulnerability of Medicaid beneficiaries and possible inadequacies in the process of care.
    Cancer 12/2011; 118(17):4271-9. · 5.20 Impact Factor
  • Renata Costa, Robert Wesolowski, Derek Raghavan
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    ABSTRACT: Advanced adrenal carcinoma remains a significant therapeutic challenge, with conventional approaches to systemic therapy having failed to achieve sustained objective remissions or major survival benefit in most instances. Several systemic therapies, including mitotane, suramin and gossypol, as well as cytotoxic agents, such as cisplatin and etoposide, have produced responses of ≈15-30%, with median survival figures of ≈6-15 months, depending on case selection bias, with only <10% 5-year survival rates. Recent preclinical and pathological studies have indicated a range of potential targets for drugs, including WNT/beta-catenin, epidermal growth factor receptor, RAF and k-RAS; similar applications in melanoma and renal carcinoma have achieved significant gains, and these targets are worthy of further, structured investigation. Advanced adrenal carcinoma constitutes an orphan disease, with a high mortality rate, and merits investment in clinical trials.
    BJU International 08/2011; 108(10):1546-54. · 3.05 Impact Factor
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    ABSTRACT: Retrospective studies suggest that p53 alteration is prognostic for recurrence in patients with urothelial bladder cancer and predictive for benefit from combination methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) adjuvant chemotherapy. Patients with pT1/T2N0M0 disease whose tumors demonstrated ≥ 10% nuclear reactivity on centrally performed immunohistochemistry for p53 were offered random assignment to three cycles of adjuvant MVAC versus observation; p53-negative patients were observed. By using a log-rank test with one-sided α = .05 and β = .10, 190 p53-positive patients were planned to be randomly assigned to detect an absolute improvement in probability of recurring by 3 years from 0.50 to 0.30. A total of 521 patients were registered, 499 underwent p53 assessment, 272 (55%) were positive, and 114 (42%) were randomly assigned. Accrual was halted on the basis of the data and safety monitoring board review of a futility analysis. Overall 5-year probability of recurring was 0.20 (95% CI, 0.16 to 0.24) with no difference on the basis of p53 status. Only 67% of patients randomly assigned to MVAC received all three cycles with 12 patients receiving no treatment. There was no difference in recurrence in the randomly assigned patients (hazard ratio, 0.78; 95% CI, 0.29 to 2.08; P = .62). Neither the prognostic value of p53 nor the benefit of MVAC chemotherapy in patients with p53-positive tumors was confirmed, but the high patient refusal rate, lower than expected event rate, and failures to receive assigned therapy severely compromised study power.
    Journal of Clinical Oncology 08/2011; 29(25):3443-9. · 18.04 Impact Factor
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    ABSTRACT: This article presents the long-term results of the international multicenter randomized trial that investigated the use of neoadjuvant cisplatin, methotrexate, and vinblastine (CMV) chemotherapy in patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy. Nine hundred seventy-six patients were recruited between 1989 and 1995, and median follow-up is now 8.0 years. This was a randomized phase III trial of either no neoadjuvant chemotherapy or three cycles of CMV. The previously reported possible survival advantage of CMV is now statistically significant at the 5% level. Results show a statistically significant 16% reduction in the risk of death (hazard ratio, 0.84; 95% CI, 0.72 to 0.99; P = .037, corresponding to an increase in 10-year survival from 30% to 36%) after CMV. We conclude that CMV chemotherapy improves outcome as first-line adjunctive treatment for invasive bladder cancer. Two large randomized trials (by the Medical Research Council/European Organisation for Research and Treatment of Cancer and Southwest Oncology Group) have confirmed a statistically significant and clinically relevant survival benefit, and neoadjuvant chemotherapy followed by definitive local therapy should be viewed as state of the art, as compared with cystectomy or radiotherapy alone, for deeply invasive bladder cancer.
    Journal of Clinical Oncology 06/2011; 29(16):2171-7. · 18.04 Impact Factor

Publication Stats

7k Citations
1,534.17 Total Impact Points

Institutions

  • 2011–2014
    • Carolinas HealthCare System
      Charlotte, North Carolina, United States
    • Case Western Reserve University
      • Department of Epidemiology and Biostatistics
      Cleveland, OH, United States
    • The Ohio State University
      Columbus, Ohio, United States
  • 2012
    • University of Leicester
      • Department of Cancer Studies and Molecular Medicine
      Leicester, ENG, United Kingdom
  • 2005–2011
    • Cleveland Clinic
      Cleveland, Ohio, United States
  • 2009
    • American Cancer Society
      Atlanta, Georgia, United States
  • 2008
    • Dana-Farber Cancer Institute
      • Lank Center for Genitourinary Oncology
      Boston, MA, United States
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 2006
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 2004–2006
    • Columbia University
      New York City, New York, United States
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 2000–2006
    • Oregon Health and Science University
      • Division of Hematology & Medical Oncology
      Portland, OR, United States
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
  • 2000–2005
    • University of Southern California
      • Department of Urology
      Los Angeles, California, United States
  • 2003–2004
    • University of California, Los Angeles
      • • Department of Urology
      • • Division of Hematology and Medical Oncology
      Los Angeles, CA, United States
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 1991–1998
    • Roswell Park Cancer Institute
      • Department of Medicine
      Buffalo, NY, United States
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
  • 1997
    • University of Illinois at Chicago
      • Section of Hematology and Oncology
      Chicago, IL, United States
    • University of Chicago
      Chicago, Illinois, United States
  • 1983–1993
    • Royal Prince Alfred Hospital
      • • Department of Medical Oncology
      • • Department of Radiation Oncology
      Camperdown, New South Wales, Australia
  • 1980–1993
    • University of Sydney
      • NHMRC Clinical Trials Centre (CTC)
      Sydney, New South Wales, Australia
  • 1992
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 1987
    • Concord Hospital
      Concord, New Hampshire, United States
    • Royal North Shore Hospital
      Sydney, New South Wales, Australia
  • 1983–1987
    • Ludwig Institute for Cancer Research Australia
      Melbourne, Victoria, Australia
  • 1982
    • Ludwig Institute for Cancer Research
      La Jolla, California, United States
  • 1981
    • Ludwig Institute for Cancer Research Sweden
      Uppsala, Uppsala, Sweden