177 LU PSMA THERAPY OF PROSTATE CANCER INITIAL EXPERIENCE. Dr.SHAGOS.G.S. DRM, DNB,MNAMS, FEBNM ASTER MEDCITY.

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1 177 LU PSMA THERAPY OF PROSTATE CANCER INITIAL EXPERIENCE Dr.SHAGOS.G.S. DRM, DNB,MNAMS, FEBNM ASTER MEDCITY.

2 PROSTATE CANCER :MAGNITUDE OF PROBLEM ADENOCARCI NOMA PROSTATE:

3 TREATMENT OPTIONS DEPENDS ON STAGING,GLEASONS SCORE. LOCALISED DISEASE, LOW RISK : SURGERY / RADIATION THERAPY. INTERMEDIATE RISK: NEOADJUVANT ADT + SURGERY / R.T (EBRT OR BRACHYTHERAPY). SURGERY POSITIVE SURGICAL MARGINS ADJUVANT R.T

4 HIGH RISK /LOCALLY ADVANCED -NEOADJ ADT + RADICAL R.T + ADJUVANT ADT. - RADICAL PROSTATECTOMY + PELVIC LYMPHADENECTOMY.

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7 INITIAL RESPONSE TO ANDROGEN DEPRIVATION THERAPY IS USUALLY GOOD. DEVELOPMENT OF ANDROGEN RESISTANCE LEADS TO PROGRESSIVE DISEASE MAJOR REASON FOR MORBIDITY AND MORTALITY. METASTATIC DISEASE- ADT, ORCHIECTOMY, CHEMOTHERAPY.

8 CHEMOTHERAPY (DOCETAXEL,ABIRATERONE, ENZALUTAMIDE, CABAZITAXEL), 223 RADIUM CHLORIDE TARGETED RADIONUCLIDE THERAPY

9 Metastatic disease treatment algorithm Published: 22 September Authors:C. Parker1, S. Gillessen2 & A. Horwich3 on behalf of the ESMO Guidelines Committee 1Royal Marsden Hospital, Sutton, UK; 2Department of Oncology/Hematology, Kantonsspital St Gallen, St Gallen, Switzerland; 3The Institute of Cancer Research, London, UK

10 TARGETED RADIONUCLIDE THERAPY METASTATIC CASTRATION RESISTANT PROSTATE CANCER-TARGETS PSMA :TRANSMEMBRANE PROTEIN WITH INCREASED EXPRESSION IN PROSTATE CA. TARGETED DELIVERY OF THERAPEUTIC RADIATION TO ALL METASTATIC SITES, DELIVERS HIGH RADIATION DOSE SPARING NORMAL TISSUES. HIGH ABSORBED TUMOUR DOSES(3.3.mGy/MBq).

11 177 LUTETIUM 177Lu- MEDIUM ENERGY BETA EMITTER, MAX ENERGY 0.5 MeV. MAX TISSUE PENETRATION 2 MM. T1/2 6.7 DAYS. γ-rays: 208 (10%) & 113 kev (6%) ABUNDANCE. SHORTER BETA RANGE-BETTER IRRADIATION OF SMALL

12 PREPARATION Water heater baths switched on for 90 Degrees Transfer 900 micro liter of Buffer Solution to the Eliqort containing 100micor liter of Peptide. Transfer the mixture of Buffer and Peptide to a Syringe. Push this Syringe to the Vial of Lu 177. Pull back the same volume of Air into the syringe Without removing the Syringe from the vial and push air back into the Lu177 Vial. Remove syringe from vial & transfer the vial to the heater bath. Heat the Lu 177 Vial for 25 minutes at 90 Degrees.

13 QUALITY CONTROL of 177Lu-Peptides Chemical purity checked by TLC Put a drop of product on the TLC(silica gel) sheet- sheet placed in a centrifuge tube containing mobile phase(sodium citrate buffer) with activity spot near mobile phase. When mobile phase is close to the end of TLC sheet the sheets are cut into two pieces(in between mobile phase front and drop added) Measure activity- activity at bottom represents labelled product whereas upper part represents impurities as impurities move with mobile phase The purity is ok when A bottom/ (A bottom +A top) 95%

14 PRE THERAPY CHECKLISTS PRETHERAPY IMAGING SHOULD SHOW GOOD LOCALISATION OF GALLIUM PSMA LIGAND IN METASTATIC SITES. DTPA RENOGRAM COMPLETE BLOOD COUNT. BASELINE PSA LEVELS.

15 TECHNIQUE PRE THERAPY HYDRATION, PREMEDICATION, COLD COMPRESS TO PAROTIDS. AMINOVEN 10% IV : 1 BOTTLE PRIOR TO THERAPY, 200 ML/ HR X 3 BOTTLES AFTER THERAPY. IV 177 LUTETIUM PSMA OVER 20 MINUTES.HYDRATION CONTINUED.

16 CASE SCENARIO 1 66 YR OLD,CAD, D.M, DIAGNOSED WITH METASTATIC CA PROSTATE 2003 ( MRI: T4a LESION WITH PARA-AORTIC & LEFT ILIAC NODAL METS). SKELETAL LESIONS IN PELVIS/ FEMUR AND ALL VISUALIZED VERTEBRAE. PSA: 100. B/L ORCHIDECTOMY, switched different hormonal drugs as the PSA trend changed.

17 Bone scan - all vertebrae/ shoulder/ribs/ hip joints, upper 1/3 of both femur R>>L. on Zoledronic acid Q Monthly since SYMPTOMATIC : Pain in right hip joint, severe pain which reduces only with a NSAID (Aceclofenac) PSA is trending upward, Breakthrough disease. GALLIUM PSMA PET CT SKELETAL, HEPATIC, NODAL AND PULMONARY METS.

18 initiated on Inj. Cabazitaxel, Q3WEEKLY with daily Prednisolone. EXTERNAL R.T TO RIGHT HEMIPELVISMINIMAL SYMPTOMATIC RELIEF. RISING PSA LEVELS, INCREASINGLY SYMPTOMATIC. Repeat Gallium PSMA : Increase in number & size of PSMA over expressing lymph nodes,mixed response in skeletal lesions with increase in number of skeletal

19 PRE THERAPY PSA 33.7 ng/ml. DTPA renogram :-No PUJ/VUJ obstruction. Serum Creatinine, CBC -WNL. 1ST SITTING : 7400 MBQ of 177 LU PSMA

20 SERUM PSA INITIAL 33 CAME DOWN TO 2.5 AFTER 1 SITTING. INCREASED TO 37 NG/ML AFTER 2ND SITTING. GA PSMA AFTER 2 SITTINGSMIXED RESPONSE IN SKELETAL, GOOD RESPONSE IN NODAL AND LIVER LESIONS SHOWED PROGRESSION.

21 SYMPTOMATIC RELIEF EXCELLENT WITH RESPECT TO SKELETAL METS-PAIN SCORE 3. NODES RESPONDED WELL. LIVER LESIONS UNRESPONSIVE. RELIEF IN PAIN LASTED FOR 5 MONTHS.SIGNIFICANT IMPROVEMENT IN QOL. AFTER 3RD SITTING DEVELOPED BONE MARROW

22 CASE SCENARIO # 2 MILD RENAL FAILURE 81 yr old gentleman,adenocarcinoma prostate, bilateral orchidectomy in 2006 and was on bicalutamide later on. CHRONIC D.M, POST CABG in TOOK Honvan tablets FOR A WHILE. Abiraterone along with zolendronic acid started in April 2015.

23 Gallium scan :GA PSMA AVID residual prostate CA + multiple supra & Infradiapghramatic lymph nodal, b/l pulmonary, liver and extensive skeletal mets. OLD age,progressive symptomatic disease-- not keen on giving chemotherapy-referred for 177 Lutetium PSMA therapy

24 DTPA renogram :PUJ non obstructed LT kidney (FN:79%). Hydronephrotic NON OBSTRUCTED RT kidney(fn:21 %).Total GFR :67 ml/min. S.creat :1.55 mg/dl. S.PSA PRE therapy101.6 ng 170MBQ OF 177 LU PSMA (AMINOVEN GIVEN) NON RESPONDER TO THERAPY. POST THERAPY: NO DETERIORATION IN RENAL FUNCTION ON FUP FOR 3 MONTHS.

25 CASE SCENARIO # 3 73 YR OLD diagnosed with adenocarcinoma prostate in 2014 aug. (S.PSA level of 100 n/ml). Sep 2014, started on Leupride+Tabi: PSA reached nadir at 2ng/ml in Dec,2015. started on Tab abiraterone later on. Serum PSA levels started slowly and serially rising.

26 Gallium PSMA avid primary prostate & multiple avid and non avid skeletal metastases. PSMA non avid hypodense lesion in segment VIII of liver. S.PSA :112 ng/ml MBq of 177 Lu PSMA. requirements for pain killers came down significantly. PAIN SCORE FROM 4 TO 0. s.psa ng/ml

27 2nd sitting : 6290 MBq of 177 Lutetium PSMA after 3 months. POST THERAPY PSA IS 2 NG/ML

28 FOLLOW UP GALLIUM SCAN AFTER 2CYCLES NEAR COMPLETE RESOLUTION OF ALMOST ALL SKELETAL AND NODAL DISEASE-PAIN FREE. NO NEW SKELETAL LESIONS. INCREASE IN SIZE OF NON AVID LIVER LESION SHOWING MILD AVIDITY NOW. AFP 10 BIOPSY : HCC

29 CASE SCENARIO # 4 MARROW METS 73 YR OLD GENTLEMAN. OBSTRUCTIVE LUTS, NO COMORBIDITIES. ELEVATED PSA : 126 ng/dl BONE SCAN EXTENSIVE SKELETAL METS, MARROW INVOLVEMENT.

30 PRE THERAPY BONE SCAN PRE THERAPY GALLIUM SCAN

31 GALLIUM PSMA SCAN: PRIMARY DISEASE + PREDOMINANTLY SKELETAL AND MARROW METS. EXTERNAL R.T TO PELVIC REGION- MILD PAIN RELIEF. LUTETIUM PSMA TAILORED DOWN DOSE : 150 MCI. POST THERAPY : SIGNIFICANT PAIN POST THERAPY,NO POST TREATMENT SCAN.

32 FOLLOW UP MARROW TOXICITY AT 4 WEEKS, REQUIRING MULTIPLE PACKED RBC, PLATELETS TRANSFUSED. NEUTROPAENIC FEVER.GRADUALLY RECOVERING. 8 WEEKS PAIN SCORE: 2. PSA :100- MILD REDUCTION?FIT TO BE TREATED AGAIN

33 LESSONS LEARNT.. MAJOR SIDE EFFECTS NONE SYMPTOMATIC PAIN RELIEF IMPROVED QUALITY OF LIFE ( HAPPY PATIENTS WHO CRAVE FOR MORE LUTETIUM AND NO CHEMO EVER AGAIN PLEASE!!!) SAFE EVEN IN MILD RENAL FAILURE BUT WITH NO OBSTRUCTIVE NEPHROPATHY

34 LESSONS LEARNT.. SKELETAL METASTASES +/ - NODES- RESPONDS WELL. MARROW TOXICITY WELL TOLERATED AT A DOSE OF mci. EXCEPTION- PREDOMINANTLY MARROW METASTASES. MARROW METS: MARROW DEPRESSION AT 4-6 WEEKSREVERSIBLE.

35 LINGERING QUESTIONS EXTENSIVE HEPATIC METASTASES- IS IT WORTH GOING AHEAD?? IF NO RESPONSE AFTER FIRST SITTING, SHOULD WE GO AHEAD WITH NEXT SITTING. THERAPY AT 8 WEEKS INTERVAL OR 12 WEEKS? WHEN DO WE CALL IT A STOP BIOCHEMICAL RESPONSE, SYMPTOMATIC RELIEF OR GALLIUM SCAN

36 LINGERING QUESTIONS. CAN WE STOP ABIRATERONE, ENZALUTAMIDE ETC ONCE PATIENT IS STARTED ON THERAPY. ADDED EFFICACY IF COMBINED WITH DOCETAXEL -? SCIENTIFIC EVIDENCE. IF SO WHAT DOSAGE AND INTERVAL?

37 Searching for answers quest continues.. Thank you!