Temozolomide As A Radiosensitizer Clinical Experience At Kmio
Upcoming SlideShare
Loading in...5
×
 

Temozolomide As A Radiosensitizer Clinical Experience At Kmio

on

  • 1,562 views

 

Statistics

Views

Total Views
1,562
Views on SlideShare
1,562
Embed Views
0

Actions

Likes
1
Downloads
11
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Temozolomide As A Radiosensitizer Clinical Experience At Kmio Temozolomide As A Radiosensitizer Clinical Experience At Kmio Presentation Transcript

    • TEMOZOLOMIDE AS A RADIOSENSITIZER -CLINICAL EXPERIENCE AT KMIO. Dr. B. Krishnamurthy Reddy, Dr.V.Lokesh, Dr.Vijaybhaskar Prof & Head Radiation Oncology Kidwai Memorial Institute of Oncology BANGALORE.
    • BRAIN TUMORS AT KMIO 1998
      • Total: 213 out of 7062 new patients ( 3%)
      • Male:131, Female: 52 & Children:30
      • Grade III /IV Astrocytomas 50% : 90,
      • Astrocytoma unclassified:29
      • Brainstem Glioma:13,Ependymoma:5
      • Oligodendroglioma:9,
      • Medulloblastoma:10, Craniopharyngioma:4, Brain Mets:23,Others=30
      • (Pitutary , Pinealoblastoma, Lymphoma, cerebella Astrocytoma & Others).
    • TREATMENT OPTIONS & OUT COME AT K.M.I.O
      • SURGERY : Biopsy/Subtotal/Near .total Excision.
      • RADIOTHERAPY: GTV with 2 to 3 cms clearance 60 Gy @ CF.
      • CHEMOTHERAPY +- CT : Nitrosoureas.
      • Results : Med- Survival: GBM<1 year (8 mo) AA: 2years
    • FACTORS INFLUENCING FAVOURABLE OUTCOME IN GLIOMAS
          • Younger Age; Low Grade; Good K.P.S (>80);
          • Oligodendroglioma with Ch. 1p and 19 q loss.
          • Adequate surgery & P.O.R.T
          • Temozolomide as Concurrent & Adjuvant (>2001)
    • CONCOMITANT & ADJUVANT TEMOZOLAMIDE WITH RADIOTHERAPY FOR NEWLY DIAGNOSED Gr.III / Gr.IV GLIOMAS ,
      • Investigator initiated study
      • (2002 – 2006)
      • Department of Radiation Oncology; K.M.I.O, Bangalore.
    • RATIONALE FOR THE STUDY
      • Proved efficacy : in vitro: additive and synergistic activity.
      • 1. TMZ+Concurrent RT :
      • Demonstrated additive cytotoxicity against W 373 MG GBM cell Line (with low AGT (alkylguanine, alkyl transferase enzyme) expression.)
      • (Wedge SR, Anticancer Drugs 8: 92-97, 1997)
      • 2. TMZ shown to induce G2-M arrest in gliomacells,
      • thus synchronizing the cell cycle in a radiosensitive phase.
      • (Hirose Y: Cancer Res: 61:1951-1963, 2001)
    • RATIONALE FOR THE STUDY contd..
      • Proved efficacy : in vivo: additive and synergistic activity .
      • Phase II Trial in rec. GBM:
      • Objective R.R. 8%, overall RR: 53%, 6 months . PFS=18% & O.S=46%.
      • TMZ was well tolerated with Grade ¾ Neutropenia & Thrmbocytopenia < 10
      • (Bradey M: Ann oncology. 12:259-2366, 2001)
      • 2. Pre-RT TMZ in newly GBM: RR=43% (CR-9%) (Friedman et al)
      • Report of OS at 1 yr : 58%, at 2 yr:
      • 31% in newly GBM with concurrent & adj.TMZ
      • (R.Stupp et al in J.of cli.oncol. 20: 1375-1328, 2002)
      • 4. Oral Administration:
      • 100% of bioavailability, readily crosses the BBB.with plasma-CSF Ratio of 30%.
    • OBJECTIVES:
      • To evaluate the efficacy & safety
      • To Improve survival
    • ELIGIBILITY:
      • Newly diagnosed HGG (Gr III , IV)
      • Adequate bone marrow, hepatic, renal function
      • No other severe underlying disease
      • Written informed consent
    • TRIAL DESIGN :
      • Page: 11 9
    • Patients Charecteristics treated with TMZ with RT
      • Patients Treated : 14
      • Female : 8
      • Male : 6
      • Mean Age : 40 (18-65)
      • Mean KPS : 70 (60-90)
      • GBM : 4
      • AA : 5
      • AO : 5
      • Surgery:
      • Biopsy : 2
      • Craniotomy & Decompression : 11
      • Near total excision : 1
      • TMZ:
      • Only Concurrent : 6
      • Concurrent & Adjuvant : 8
      Patients Charecteristics treated with TMZ with RT (contn..)
      • Evaluation of Response:
      • Only Clinical : 6
      • Clinical & MRI : 1
      • Clinical & CT Scan : 7
      Patients Charecteristics treated with TMZ with RT (contn..)
    • Toxicity:
      • Hematological :
        • Concurrent : nil
        • Adjuvant : Leukopenia - 2 (14%)
      • Non Hematological: nil
    • Response to Treatment
      • CR : 6
      • PR : 2
      • SD : 1
      • PD & dead : 5 (3 – AA, 2- GBM)
    • CASE NO: 2 (OS: 26 mo, CR : 8mo )
    • CASE NO: 4 (OS: 26 mo, CR : 4mo )
    • CASE NO: 11 (OS: 9 mo, near CR : 3mo )
    • SURVIVAL DATA Follow up - 100% Mean follow up - 15 ( 7 - 26mo) Alive - 9 Mean PFS - 13.5 mo Mean OS - 15.29 mo 1 Year Survival - 75% 2 Years O. Survival - 53% 2 Years PFS - 64%
    • os
    • PFS
    • SURVIVAL VS INFLUENCING FACTORS
      • Variable n mean mo 1yr. % 2Yr. %
      • n 14 13.5 75% 53%
      • ANA.A 10 16.90 * *
      • GBM 4 11.25
      • CCT & Ad. 8 14.88 * *
      • Only CCT 6 15.83
      • (* Case members limited)
    • CONCLUSION
      • TMZ in concurrent & Adjuvant setting with RT is safe & well tolerated
      • Estimated mean survival is 13.5 mo
      • 2 year survival is 53%
    • Thank You