Hematologists, Oncology Specialist (cancer)
23 years of experience
Video profile
Accepting new patients
900 Centennial Blvd
Voorhees, NJ 08043
856-325-6750
Locations and availability (6)

Education ?

Medical School
Universite Saint-Joseph (1987)
Foreign school

Awards & Distinctions ?

Awards  
Castle Connolly America's Top Doctors® (2009, 2011 - 2014)
Castle Connolly America's Top Doctors® for Cancer (2009, 2011 - 2012, 2014)
Associations
American Board of Internal Medicine
American Society of Clinical Oncology

Affiliations ?

Dr. Hageboutros is affiliated with 9 hospitals.

Hospital Affilations

Score

Rankings

  • Cooper University Hospital *
    Medical Oncology
    1 Cooper Plz, Camden, NJ 08103
    • Currently 4 of 4 crosses
    Top 25%
  • Our Lady Of Lourdes Medical Center
    Medical Oncology
    1600 Haddon Ave, Camden, NJ 08103
    • Currently 2 of 4 crosses
  • Virtua West Jersey Hospital - Voorhees
    94 Brick Rd, Marlton, NJ 08053
    • Currently 2 of 4 crosses
  • Lourdes Medical Center of Burlington County
    218A Sunset Rd, Willingboro, NJ 08046
    • Currently 1 of 4 crosses
  • Kennedy Memorial Hospital
  • Virtua Health-Voorhees Division
  • Cooper Medical Center
  • Cooper Hospital Umc
  • Cooper Hospital/U M C
  • * This information was reported to Vitals by the doctor or doctor's office.

    Publications & Research

    Dr. Hageboutros has contributed to 10 publications.
    Title Adie's Pupils in Paraneoplastic Ganglionopathy with Anna-1.
    Date January 2007
    Journal Clinical Neurology and Neurosurgery
    Excerpt

    Autonomic disturbances are common in patients with paraneoplastic syndromes associated with type-1 antineuronal nuclear autoantibodies (ANNA-1), although pupillary disturbances are infrequent. The authors describe a patient with ANNA-1 associated paraneoplastic sensory neuronopathy and bilateral Adie's pupils.

    Title Phase I Study of Sequential Administration of Topotecan and 5-fluorouracil in Patients with Advanced Malignancies.
    Date September 2002
    Journal Cancer Investigation
    Excerpt

    Topotecan is a topoisomerase-I inhibitor, a drug that stabilizes a covalent complex of enzymes and causes strand cleavage of DNA. 5-Fluorouracil (5FU) is an antimetabolite that interferes with DNA synthesis. Preclinical studies using human cancer cell line models have shown potential therapeutic synergy between these two drugs by showing the maximum cytolytic effect using sequential 5FU followed by topotecan. In the current study, 5FU was used at a fixed dose of 375 mg/m2 given intravenously for five consecutive days on a 28 day cycle. Topotecan was dose-escalated in cohorts of patients from 0.5 to 1.0 mg/m2 given intravenously for 5 days after the 5FU dose. Eleven patients were entered at different dose levels. Both hematological and gastrointestinal toxicity were dose limiting. Diarrhea was the dose-limiting toxicity at the dose of 0.75 mg/m2 of topotecan. Two cases of grade 4 neutropenia were also observed at this dose level. One patient with small cell lung cancer had a complete response, while one patient with metastatic colorectal cancer had a partial remission. Three other patients had stable disease, lasting between 6 and 8 months. Overall, the regimen was well tolerated. A phase II study using a dose of 5FU at 375 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously over 5 days every 28 days is recommended.

    Title Life-threatening Toxicity in a Dihydropyrimidine Dehydrogenase-deficient Patient After Treatment with Topical 5-fluorouracil.
    Date October 1999
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    In humans, 80-90% of an administered dose of 5-fluorouracil (5-FU) is degraded by dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2), the initial rate-limiting enzyme in pyrimidine catabolism. Cancer patients with decreased DPD activity are at increased risk for severe toxicity including diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity, and, in some cases, death. We now report the first known cancer patient who developed life-threatening complications after treatment with topical 5-FU and was shown subsequently to have profound DPD deficiency. RT-PCR and genomic PCR methodologies were used to identify a G to A mutation in the GT 5' splicing recognition sequence of intron 14, resulting in a 165-bp deletion (corresponding to exon 14) in this patient's DPD mRNA. Immunoprecipitation and Western blot analysis were then used to demonstrate that the aberrant DPD mRNA is translated into a nonfunctional DPD protein that is ubiquitinated. We conclude that the presence of this metabolic defect combined with topical 5-FU (a drug demonstrating a narrow therapeutic index) results in the unusual presentation of life-threatening toxicity after treatment with a topical drug. These data further suggest that degradation by the ubiquitin-proteosome-mediated system plays a role in the elimination of the DPD protein.

    Title Phase I Trial of Fluorouracil Modulation by N-phosphonacetyl-l-aspartate and 6-methylmercaptopurine Ribonucleoside (mmpr), and Leucovorin in Patients with Advanced Cancer.
    Date August 1997
    Journal Investigational New Drugs
    Excerpt

    The results of several clinical trials support the hypothesis that biochemical modulation may enhance the antitumor activity of 5-Fluorouracil (5-FU). We have performed a phase I trial using a combination of three different biochemical modulators at the optimal dose established in previous clinical trials. The modulators include: phosphonacetyl-l-aspartate (PALA), which may increase 5-FU incorporation into RNA; leucovorin, which potentiates thymidylate synthase inhibition; and 6-methylmercaptopurine riboside (MMPR), which promotes the intracellular retention of fluorinated nucleotides. The treatment regimen consisted of PALA 250 mg/m2 day 1, followed 24 h later by MMPR 150 mg/m2 as an iv bolus, and the initiation of a 24-hour infusion of 5-FU along with leucovorin 50 mg/m2. This regimen was repeated weekly. Doses of 5-FU were escalated in cohorts of four or more patients from 2,000 to 2,600 mg/m2. Among 20 patients entered, the majority had colorectal cancer, and most had received prior 5-FU treatment. Toxicity was predominantly gastrointestinal, and diarrhea was dose-limiting at a 5-FU dose of 2600 mg/m2. There were three partial remissions observed, two of whom had colorectal cancer. Emerging data that casts doubt on the modulation value of PALA at this dose and schedule suggests that revision of this regimen be considered before Phase II trial.

    Title The Treatment of Relapsed or Refractory Intermediate Grade Non-hodgkin's Lymphoma with Autologous Bone Marrow Transplantation Followed by Cyclosporine and Interferon.
    Date April 1997
    Journal Bone Marrow Transplantation
    Excerpt

    In an effort to decrease the relapse rate following autologous bone marrow transplantation for non-Hodgkin's lymphoma, patients were given cyclosporine and interferon following autologous marrow transplantation. Forty patients with intermediate grade non-Hodgkin's lymphoma that was relapsed or refractory to standard chemotherapy underwent autologous marrow transplantation. The preparative regimen consisted of cyclophosphamide 6.8 g/m2, etoposide 1600 mg/m2, and carmustine 400 mg/m2 over 4 days followed by reinfusion of bone marrow. Intravenous cyclosporine was started on day -1 as a 16 mg/kg loading dose followed by 3.6 mg/kg/day for 28 days after transplant. Patients were begun on alpha-interferon (starting dose, 0.5 million units s.c. every other day) following platelet engraftment (median day 24 post-transplant) and continued on 1.5 million units s.c. daily for 2 years. Regimen-related toxicities resulted in four (10%) deaths. Twenty-one (53%) patients developed marked erythema of the palms, soles, and arms. Biopsies of the erythema were consistent with grade I GVHD. Patients who did not develop rashes were not biopsied. The erythema persisted for a median of 10 days and resolved in all cases without treatment. Visceral GVHD was not apparent. All patients have been followed for a median of 24 months (range 12-54 months). To date, only five patients (13%) have relapsed after bone marrow transplant. Multivariant analysis could not identify risk factors for relapse post-transplant. Disease-free survival of all patients is 77% (95% confidence interval, 67-93%). The results of this pilot study suggest that the administration of cyclosporine and interferon may decrease the relapse rate of relapsed/refractory non-Hodgkin's lymphoma following autologous bone marrow transplantation.

    Title Involvement of Activator Protein-1 and Nuclear Factor-kappab Transcription Factors in the Control of the Dt-diaphorase Expression Induced by Mitomycin C Treatment.
    Date March 1997
    Journal Molecular Pharmacology
    Excerpt

    The antitumor antibiotic mitomycin C is activated by several bioreductive enzymes, including DT-diaphorase. In HT29 cells, mitomycin C treatment results in the induction of DT-diaphorase as reflected in elevated steady state DT-diaphorase mRNA levels. An increase in the transcriptional rate was demonstrated by nuclear run-on assay. To investigate the molecular basis of the change in transcriptional activity caused by mitomycin C treatment, electrophoretic mobility shift assays were used to demonstrate the induction of nuclear factor binding to elements in the 5' flanking region of the DT-diaphorase gene. Treatment of HT29 cells with mitomycin C resulted in the dose-dependent induction of binding activity directed to the activator protein-1 (AP-1) binding element with a time course similar to that of mRNA elevation. Supershift assays using specific antibodies to Jun and Fos demonstrated the participation of both proteins in the binding activities generated. A binding activity for the nuclear factor-kappaB (NF-kappaB) site was induced with a similar time course. Both competitor and supershift experiments indicated that a heterodimer of the NF-kappaB proteins p50 and p65 was contained in the bound complex. To further investigate the functional consequences of such binding, we transfected HT29 cells with a plasmid containing 3 kb of the DT-diaphorase 5' region upstream of a reporter gene, chloramphenicol acetyltransferase. Treatment with mitomycin C resulted in a 5.5-fold increase in the expression of a chloramphenicol acetyltransferase construct containing 3 kb of DT-diaphorase promoter sequence. Using a series of deletion mutations based on this full-length construct, we found that two regions of the DT-diaphorase promoter region, positions -346 to -588 (containing the AP-1 element) and positions -785 to -890 (containing the NF-kappaB element) are required for the full expression of the mitomycin C response. The specific involvement of these binding elements was confirmed using mutational analysis. The results demonstrate that mutation of either element alone or of both diminishes the response, indicating an additive interaction between the elements at a minimum. However, inducibility characterizes a promoter fragment as small as 78 base-pairs from the transcription start site. Treatment of cells with mitomycin C induced binding to a 38-base-pair region (-40 to -78) devoid of known transcription factor binding elements. These data suggest that mitomycin C induces the overexpression of DT-diaphorase through a mechanism involving both the AP-1 and NF-kappaB response elements and that inducibility depends on a novel factor binding element.

    Title Acute Encephalopathy Attributed to 5-fu.
    Date November 1996
    Journal Pharmacotherapy
    Excerpt

    Acute encephalopathy attributable to 5-fluorouracil (5-FU) is rare. A patient experienced this reaction associated with a continuous 5-FU infusion. The etiology of the event remains uncertain, but it is generally reversible and does not preclude retreatment with 5-FU at reduced dosages. Steroids and thiamine may expedite neurologic recovery.

    Title Phase I Trial of Fluorouracil Modulation by N-phosphonacetyl-l-aspartate and 6-methylmercaptopurine Ribonucleoside.
    Date January 1996
    Journal Cancer Chemotherapy and Pharmacology
    Excerpt

    Inhibition of pyrimidine and purine synthesis has been demonstrated to potentiate 5-fluorouracil (5-FU) activity in preclinical models. Low-dose phosphonacetyl-L-aspartate (PALA) potentiates the incorporation of 5-FU into RNA, without detectably increasing its toxicity. 6-Methylmercaptopurine riboside (MMPR) results in inhibition of purine biosynthesis with elevation of phosphoribosyl pyrophosphate (PRPP), which in turn is believed to increase the phosphorylation and intracellular retention of 5-FU. We conducted a phase I clinical trial to determine the maximum tolerated dose of 5-FU in combination with low-dose PALA and a biochemically-optimized dose of MMPR. The regimen consisted of PALA 250 mg/m2 given on day 1, followed 24 h later by MMPR 150 mg/m2, and escalating doses of 5-FU from 1625 to 2600 mg/m2 by 24 h continuous infusion. This regimen was repeated weekly. A group of 29 patients with a diagnosis of malignant solid tumor were entered; their median performance status was 1. The dose-limiting toxicity was mucositis, while other gastrointestinal toxicity was minimal. Two patients also experienced ischemic chest pain during the 5-FU infusion. The maximum tolerated dose of 5-FU in this combination was 2600 mg/m2. Several responses were observed including a complete remission in a previously treated breast cancer patient and two partial responses in breast and colon cancer. MMPR pharmacokinetics were obtained from urine analyses in 21 patients on this trial; there was no correlation between the pharmacokinetics of MMPR and the toxicity observed. This regimen was well tolerated and phase II trials are warranted using PALA 250 mg/m2, MMPR 150 mg/m2, and 5-FU 2300 mg/m2 by continuous infusion over 24 h.

    Title Phase I Study of Phosphonacetyl-l-aspartate, 5-fluorouracil, and Leucovorin in Patients with Advanced Cancer.
    Date February 1995
    Journal Cancer Chemotherapy and Pharmacology
    Excerpt

    Low-dose phosphonacetyl-L-aspartate (PALA) may potentiate both 5-fluorouracil (5-FU) incorporation into RNA and thymidylate synthase inhibition by 5-fluorodeoxyuridylate (5-FdUMP). The gastrointestinal toxicity of 5-FU is not increased by PALA administration. Exogenous leucovorin, on the other hand, which enhances thymidylate synthase inhibition, appears to increase the clinical toxicity of 5-FU in a dose-dependent manner. As a result, the clinical use of high-dose leucovorin requires a marked dose reduction of 5-FU. Extracellular leucovorin levels of 1 microM suffice to maximize the enhancement of thymidylate synthase inhibition in several models. We conducted a trial to add leucovorin to the PALA/5-FU regimen. We chose a leucovorin dose that was predicted to yield end-infusion total reduced folate concentrations of 1 microM. The major endpoint was to determine the maximum tolerated dose of 5-FU in this combination. The regimen consisted of 250 mg/m2 PALA given on day 1 and, 24 h later, escalating 5-FU doses ranging from 1,850 to 2,600 mg/m2 admixed with 50 mg/m2 leucovorin and given by 24-h infusion. Courses were repeated weekly. A total of 24 patients with a median performance status of 1 were entered at three dose levels. Diarrhea was dose-limiting; 6/13 patients had grade II or worse diarrhea at 2,600 mg/m2. Dose modification resulted in a mean dose intensity of 2,300 mg/m2 at both the 2,600- and 2,300-mg/m2 dose levels. The 2,300-mg/m2 dose is suitable for phase II testing of this regimen. Three patients (two with breast cancer and 1 with sarcoma) had a partial remission. We measured steady-state concentrations (Css) of 5-FU in 23 patients. The mean Css increased with dose from 0.738 to 1.03 micrograms/ml. Total body clearance did not vary with dose in this range. Patients with grade II or worse diarrhea had a higher mean Css (1.10 +/- 0.19) than those with grade O or I toxicity (0.835 +/- 0.25, P < 0.02). Total bioactive folates (bound and free) were measured using a biological assay. Pretreatment values ranged from 2 to 52 nM and were not predictive of toxicity. End-infusion (23-h) values were somewhat lower than predicted and ranged from 400 to 950 nM. The risk of diarrhea was positively correlated with end-infusion total folate values. In a logistic regression analysis, total folate values obtained at 23 h were a more powerful predictor of diarrhea than were 5-FU Css values.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Extrapulmonary Small Cell: a Novel Case of Small Cell Carcinoma of the Thyroid Gland.
    Date
    Journal Medical Oncology (northwood, London, England)
    Excerpt

    Neuroendocrine tumors comprise a large group of malignancies which share unique morphological features and are characterized by the presence of neuroendocrine markers such as synaptophysin, chromogranin-A, and CD56 (N-CAM), ranging from indolent tumors, such as carcinoid tumors, to aggressive tumors, such as small cell carcinoma. The lung is the most common site for primary neuroendocrine tumors. Extrapulmonary primary sites of small cell carcinoma are rare but have been documented arising from various sites including esophagus, stomach, colon and rectum, gallbladder, thymus, salivary gland, ovary, cervix, bladder, prostate, and skin. We present a case of small cell carcinoma arising from the thyroid gland, a site not previously described in the literature. A 59-year-old woman presented with a thyroid mass, which, after resection, showed small cell morphology and positive immunostains for TTF-1, synaptophysin, chromogranin-A, CD56, etc. Five months after diagnosis, she had widely metastatic disease. After a near-complete response to the first chemo-treatment, her disease progressed. Following local radiation and more rounds of chemotherapy, she succumbed to the disease, 15 months after diagnosis. Our patient had no pulmonary lesions at the time of diagnosis to suggest metastasis from the lung. Much like its pulmonary counterparts, this small cell carcinoma of primary thyroid origin displayed an aggressive clinical course and poor outcome. Although it shows early sensitivity to chemotherapy, small cell carcinoma remains a difficult-to-treat cancer with a poor prognosis and can rarely be seen originating in organs outside of the lung.


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