R A Popescu

Publications (10)69.49 Total impact

• Article: A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response.

  J M Foran, R K Gupta, D Cunningham, R A Popescu, A H Goldstone, J W Sweetenham, R Pettengell, P W Johnson, E Bessell, B Hancock, K Summers, J Hughes, A Z Rohatiner, T A Lister
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  ABSTRACT: Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.
  British Journal of Haematology 05/2000; 109(1):81-8. · 4.94 Impact Factor
• Article: European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma.

  J M Foran, A Z Rohatiner, D Cunningham, R A Popescu, P Solal-Celigny, M Ghielmini, B Coiffier, P W Johnson, C Gisselbrecht, F Reyes, J A Radford, E M Bessell, B Souleau, A Benzohra, T A Lister
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  ABSTRACT: Mantle-cell lymphoma (MCL), immunocytoma (IMC), and small B-cell lymphocytic lymphoma (SLL) are B-cell malignancies that express CD20 and are incurable with standard therapy. A multicenter phase II study was conducted to assess the toxicity and the overall response rates (RR) and complete response (CR) rates to rituximab (chimeric anti-CD20 monoclonal antibody). Between January 1997 and January 1998, 131 patients with newly diagnosed MCL (MCL1; n = 34) and previously treated MCL (MCL2; n = 40), IMC (n = 28), and SLL (n = 29) received rituximab 375 mg/m(2)/wk for 4 weeks via intravenous infusion. Restaging studies were performed 1 and 2 months after treatment. An analysis of the duration of response was conducted in December 1998. Eleven patients were unassessable, including one who died of splenic rupture after the first infusion. The RR among the 120 assessable patients was 30% (36 of 120 patients). The RR by histology was as follows: MCL1, 38%; MCL2, 37%; IMC, 28%; and SLL, 14%. Ten patients, all with MCL, achieved CR. The median duration of response in MCL was 1.2 years. Immediate side effects were common and usually responded to adjustments in the infusion rate. There were 31 episodes of infection after treatment; most cases were mild. Cardiac arrhythmia and ophthalmologic side effects occurred in 10 and nine patients, respectively, including one case of severe loss of visual acuity. Single-agent rituximab has moderate activity in MCL and IMC but only limited activity in SLL. The duration of response in MCL was similar to that previously reported in follicular lymphoma. Its use in combination with cytotoxic chemotherapy to increase the CR rate is warranted in MCL and IMC.
  Journal of Clinical Oncology 02/2000; 18(2):317-24. · 18.37 Impact Factor
• Article: Adjuvant or palliative chemotherapy for colorectal cancer in patients 70 years or older.

  R A Popescu, A Norman, P J Ross, B Parikh, D Cunningham
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  ABSTRACT: The surgical treatment of colorectal cancer (CRC) in elderly patients (age 70 years or older) has improved, but data on adjuvant and palliative chemotherapy tolerability and benefits in this growing population remain scarce. Elderly patients are underrepresented in clinical trials, and results for older patients are seldom reported separately. Using a prospective database, we analyzed demographics, chemotherapy toxicity, response rates, failure-free survival (FFS), and overall survival (OS) of CRC patients receiving chemotherapy at the Royal Marsden Hospital. The cutoff age was 70 years. A total of 844 patients received first-line chemotherapy with various fluorouracil (5-FU)-containing regimens or raltitrexed for advanced disease, and 543 patients were administered adjuvant, protracted venous infusion 5-FU or bolus 5-FU/folinic acid (FA) chemotherapy. Of the 1,387 patients, 310 were 70 years or older. There was no difference in overall or severe (Common Toxicity Criteria III to IV) toxicity between the two age groups, with the exception of more frequent severe mucositis in older patients receiving adjuvant bolus 5-FU/FA. For patients receiving palliative chemotherapy, no difference in response rates (24% v 29%, P =.19) and median FFS (164 v 168 days) were detected when the elderly were compared with younger patients. Median OS was 292 days for the elderly group and 350 days for the younger patients (P =.04), and 1-year survival was 44% and 48%, respectively. The length of inpatient hospital stay was identical. Elderly patients with good performance status tolerated adjuvant and palliative chemotherapy for CRC as well as did younger patients and had similar benefits from palliative chemotherapy.
  Journal of Clinical Oncology 09/1999; 17(8):2412-8. · 18.37 Impact Factor
• Article: Surgery plus chemotherapy or chemotherapy alone for primary intermediate- and high-grade gastric non-Hodgkin's lymphoma: the Royal Marsden Hospital experience.

  R A Popescu, A C Wotherspoon, D Cunningham, A Norman, J Prendiville, M E Hill
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  ABSTRACT: Primary gastric lymphomas (PGL) have traditionally been treated with surgery followed by chemotherapy or radiotherapy. Surgery was thought to improve staging, optimise local disease control and reduce risk of perforation or bleeding, but recent studies question its role. In this study, patients with intermediate- or high-grade PGL who received chemotherapy from 1985 to 1996 at the Royal Marsden Hospital were identified using a prospectively accrued database. A total of 37 patients (6 with low-grade mucosa-associated lymphoid tissue lymphoma (MALT-L), 9 with high-grade MALT-L, 20 with diffuse large B-cell (DLBC) lymphoma and 2 other histologies), 17 of whom had localised disease, were treated with either surgery plus chemotherapy or chemotherapy alone. 5-year overall survival for localised and advanced PGL was 94 and 50%, respectively, with no differences between the two treatments over a 53 months median follow-up. No perforations or serious bleeding occurred. Surgery is associated with important morbidity and we detected no benefit of surgery prior to chemotherapy in this limited series of patients.
  European Journal of Cancer 07/1999; 35(6):928-34. · 5.54 Impact Factor
• Article: High-dose chemotherapy and autologous transplantation in lymphomatous polyposis in second remission: three case reports and literature review.

  R A Popescu, A C Wotherspoon, D Cunningham
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  ABSTRACT: Lymphomatous polyposis is a rare primary gastrointestinal lymphoma. It morphologically and immunohistochemically resembles mantle cell lymphoma, with which it shares a disappointing response rate and duration following conventional anthracyclin-containing combination chemotherapy, with a short median survival and virtually no long-term survivors. We report the use of high-dose chemotherapy with autologous stem cell transplantation in second partial remission in three patients with lymphomatous polyposis treated at the Royal Marsden Hospital. All patients achieved a complete response, and one patient remains well and disease-free 64 months following transplantation and 76 months after diagnosis.
  Bone Marrow Transplantation 08/1998; 22(1):103-6. · 3.75 Impact Factor
• Article: bcl-2 expression is reciprocal to p53 and c-myc expression in metastatic human colorectal cancer.

  R A Popescu, A Lohri, E de Kant, C Thiede, J Reuter, R Herrmann, C F Rochlitz
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  ABSTRACT: Apoptosis (programmed cell death) inhibition may be an important mechanism by which gastrointestinal mucosal cells containing damaged DNA evade normal clearance mechanisms and grow to become invasive tumours. Since bcl-2 is an apoptosis inhibitor, bcl-2 mRNA expression was measured in 21 metastases of colorectal cancer using reverse transcription-polymerase chain reaction analysis. The mean bcl-2 mRNA expression (0.45 U, P < 0.0001) was lower than that of normal mucosal controls (= 1 U). p53 expression was inversely correlated with bcl-2 expression (P = 0.021) in 19 evaluable samples, and in tumours where p53 expression was over twice that of normal colonic mucosal values, bcl-2 mRNA was significantly decreased (mean 0.30, P = 0.0052). c-myc was also inversely correlated with bcl-2 expression (P = 0.025). Decreased bcl-2 expression in metastatic colorectal cancer may be partly due to allelic loss, given the proximity of bcl-2 to the frequently deleted DCC gene on chromosome 18q. However, the inverse correlation to p53/c-myc suggests an active downregulation of bcl-2, possibly following delegation of its apoptosis inhibiting role to other genes.
  European Journal of Cancer 08/1998; 34(8):1268-73. · 5.54 Impact Factor
• Article: Local recurrence of a primary pancreatic lymphoma 18 years after complete remission.

  R A Popescu, A C Wotherspoon, D Cunningham
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  ABSTRACT: Primary pancreatic lymphoma is exceedingly rare, with fewer than 40 patients reported in the English literature, mostly in single case publications. It comprises under 0.2 per cent of pancreatic tumours in one surgical series, but represents a disease that may be curable even in advanced stages and thus should be distinguished from other pancreatic malignancies. We report on a patient with lymphoma initially presenting in the pancreas in 1978, achieving complete remission (CR) and re-presenting with pancreatic lymphoma 18 years after treatment, with immunohistochemical and molecular studies suggesting recurrence of the original phenotype.
  Hematological Oncology 04/1998; 16(1):29-32. · 2.47 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Chemotherapy for advanced pancreatic cancer--some light at the end of the tunnel?

  R A Popescu, D Cunningham
  Annals of Oncology 06/1997; 8(5):415-6. · 6.43 Impact Factor
• Article: New approaches to the treatment of gastro-intestinal cancer.

  J S Waters, P J Ross, R A Popescu, D Cunningham
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  ABSTRACT: A number of new cytotoxic agents are currently being assessed for the treatment of gastro-intestinal cancers. Colorectal cancer has been successfully treated with several direct thymidylate synthase inhibitors, oral 5-fluorouracil analogues, irinotecan, and oxaliplatin, alone and in combination regimens. Upper gastro-intestinal malignancies are also proving responsive to combinations including irinotecan and the taxanes. Pancreatic cancer, while remaining relatively chemoresistant, is proving treatable with the new direct thymidylate synthase inhibitors, docetaxel, and gemcitabine, improvements in quality of life being an important outcome. New strategies of treatment delivery are also proving beneficial. Neo-adjuvant chemotherapy is well tolerated for the treatment of gastric cancer and results in tumour downstaging. Randomized trials will show whether this translates into a survival advantage. Combination chemoradiation for oesophageal, pancreatic, and rectal cancers also appears to be an effective strategy. Biological therapies including hormonal manipulation, immunotherapy, angiogenesis inhibition, and gene-directed therapies are the subjects of intensive research at present, with many approaches being applied in early clinical trials. These have demonstrated the tolerability of many of these treatments with evidence for activity in some cases.
  Digestion 02/1997; 58(6):508-19. · 2.05 Impact Factor
• Article: New Approaches to the Treatment of Gastro-lntestinal Cancer

  J.S. Waters, P.J. Ross, R.A. Popescu, D. Cunningham
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  ABSTRACT: A number of new cytotoxic agents are currently being assessed for the treatment of gastro-intestinal cancers. Colorectal cancer has been successfully treated with several direct thymidylate synthase inhibitors, oral 5-fluorouracil analogues, irinotecan, and oxaliplatin, alone and in combination regimens. Upper gastro-intestinal malignancies are also proving responsive to combinations including irinotecan and the taxanes. Pancreatic cancer, while remaining relatively chemoresistant, is proving treatable with the new direct thymidylate synthase inhibitors, docetaxel, and gemcitabine, improvements in quality of life being an important outcome. New strategies of treatment delivery are also proving beneficial. Neo-adjuvant chemotherapy is well tolerated for the treatment of gastric cancer and results in tumour downstaging. Randomized trials will show wheter this translates into a survival advantage. Combination chemoradiation for oesophageal, pancreatic, and rectal cancers also appears to be an effective strategy. Biological therapies including hormonal manipulation, immunotherapy, angiogenesis inhibition, and gene-directed therapies are the subjects of intensive research at present, with many approaches being applied in early clinical trials. These have demonstrated the tolerability of many of these treatments with evidence for activity in some cases.
  Digestion 08/1970; 58(6):508-519. · 2.05 Impact Factor