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CLINICAL TRIALS IN CERVICAL CANCER Cancer Institute (WIA) experience

CLINICAL TRIALS IN CERVICAL CANCER Cancer Institute (WIA) experience. Incidence. Incidence is 24.8 per 100,000 female population - MMTR data Frequency at the Institute is 37.9% Majority of these patients (71.4%) present with advanced stages of disease . Treatment.

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CLINICAL TRIALS IN CERVICAL CANCER Cancer Institute (WIA) experience

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  1. CLINICAL TRIALSINCERVICAL CANCERCancer Institute (WIA) experience

  2. Incidence • Incidence is 24.8 per 100,000 female population - MMTR data • Frequency at the Institute is 37.9% • Majority of these patients (71.4%) present with advanced stages of disease

  3. Treatment • Surgery & radiation therapy provide excellent 5-year & 10-year survival rates for early cancers • 5-year survival rate for locally advanced carcinoma ranges from 65% (FIGO stage II B) to 5% (FIGO stage IV A)

  4. Radiotherapy • Radiation fails to control 35-90% of disease with 66% of the failures occurring in the pelvis • Failures attributed to metastatic disease outside the radiation field & large central tumor volumes resistant to local therapies

  5. Clinical trials • The limitation of radiotherapy led us on the long trail of prospective concurrent randomized placebo-controlled clinical trials, since 1960, using a variety of chemical sensitizers, cytotoxic drugs & physical agent like hyperthermia to potentiate the radiotherapeutic effect • Randomization & evaluation were blind in these trials

  6. SPI TRIAL

  7. SPI trial • Histologically confirmed squamous cell carcinoma • Stage III cervical cancers • Satisfactory general health • Patients with gross anemia, cardiac decompensation, or renal or hepatic dysfunction were excluded

  8. SPI trial • SPI & SPG are podophyllin derivatives • Dose of SPI was 400 mg in 25 ml of distilled water, injected IV slowly over 1-2 min 25-30 min before RT • Controls received 25 ml of distilled water • CBT was administered to a total tumor dose of 65 Gy in about 6-7 weeks on a 5 days a week schedule • Study patients received SPG capsules 400 mg per day orally for eight weeks after the end of RT

  9. No: / %CR p = 0.0005 Cancer 20, 5, 822-825, 1967

  10. CISPLATIN INCERVICALCANCER

  11. 4-arm trial • The objectives of the trial were to study the differential response and survival in the different arms and also to study the cost benefit in relation to the different arms

  12. 4-arm trial

  13. 4-arm trial • Histologically confirmed sq. cell carcinoma • Stages II B & III B • No previous treatment • Satisfacory PS • Age < 60 years

  14. 4-arm trial • No hydronephrosis / nonfunctioning kidney • Compensated IHD, Controlled DM & HT – No bar • Satisfactory renal, hepatic & pul. functions • Br. Asthma & emphysema – relative contraindications • Informed consent - Mandatory

  15. 4-arm trial

  16. 4-arm trial – arm - II

  17. 4-arm trial – arm - III

  18. 4-arm trial – arm - IV

  19. % 5 YR NED p = N.S.

  20. Trials world wide • Randomized trials • GOG trial • Keys et al – 1999 • Pearcey et al – 2002 • More effective regimens

  21. CLINICAL TRIAL OFORAL ETOPOSIDE & BLM WITH RTIN LOCALLY ADVANCEDCARCINOMA OF THE UTERINE CERVIX

  22. Objectives • To determine response rates, duration of response & survival following twice daily, long term, low dose oral Etoposide and 5-week, low dose BLM with concomitant RT for patients with locally advanced carcinoma of the uterine cervix • To observe the toxicity following this

  23. BLM - Eto trial • The eligibility criteria was the same as the previous trial • Stage – III.B • 2-arm trial • 75 patients in each arm • Study arm - RT with BLM & Etoposide • Control arm - RT with placebo

  24. BLM-Eto trial Oral etoposide • 25 mg twice a day • Days 1-14 of a 21-day cycle • 6 cycles Inj. Bleomycin • 5 mg / IV daily • Days 1-5 / week • 5 weeks

  25. BLM-Eto trial • 6 MV X-ray therapy - 180 cGy / #, 5 # / week to a dose of 50.4 Gy / 5½ weeks • Followed by ICA, delivering a dose of 5 Gy each, 5 applications, twice weekly

  26. No: / %CR/ %NED For CR, p <0.045 (Mantel Haenszel corrected)

  27. Toxicities • Upper GI – all patients - 74 • Alopecia – all patients – 74 • Pigmentation – 55 – 77% • Dermatitis -32 – 46% • Skin reaction – 12 – 16% • Neutropenia – Gr – II – 18%

  28. HYDROXYUREAASRADIATION SENSITIZER

  29. HU trial • 2-arm study • Only stage III B • Study arm - HU 80 mg / kg body weight per oral two hours prior to RT every Monday & Thursday • Control arm - Placebo tablets at the same time • 50 Gy to whole pelvis followed by ICA 23 Gy

  30. No: / %CR/ %NED p = NS

  31. REGIONAL HYPERTHERMIACOMBINED WITH RADIATIONIN LOCALLY ADVANCED CERVICAL CANCERS

  32. HT trial • 2 arm trial, • 50 patients in each arm • Obese patients with more than 3cm anterior abdominal wall fat thickness were excluded • Patients with pacemakers and metal objects within the treatment area were also excluded

  33. HT trial • HT immediately following RT • Once a week (Tues) • 420 C - 430C • Maintained for one hour • BP & pulse rate monitored

  34. No: / %CR/ %NED Int.J.Radiation Oncology Biol.physics 2005;61

  35. RANDOMISED TRIAL ON COMPARISON OF LDR AND HDR ICA IN CARCINOMA CERVIX

  36. LDR-HDR trial • To compare the efficacy of HDR vs. LDR intracavitary brachytherapy • to know the number of #s and dose / # that should be given at HDR, to produce the same biological effects as LDR

  37. LDR-HDR trial • Criteria of eligibility was the same as other trials • Stages II B & III B 2 arm trial • Arm – 1 – ext radiation + LDR 23Gy Dose rate at Point A 160-180cGy / Hr • Arm – 2 – ext radiation + 3 HDR 15Gy Dose rate at Point A 36-48 Gy / Hr

  38. 3-yr survival NED * Patients lost to FU taken as failures

  39. % 3 YR NED p= NS

  40. Nos:

  41. Future trials • More effective chemotherapy regimens. • Omit cisplatin.

  42. Future Trials • Non-myelosuppressive biologic response modifiers • Epidermal growth factor modulators • Vascular endothelial growth factor modulators • Cyclooxygenase 2 inhibitors • Targeting hypoxic cells

  43. THANK YOU

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