Post on 28-Dec-2015
Clinical case
HIGHLIGTHS IN ADVANCED RENAL CELL CARCINOMA MANAGEMENTRoma, 24 febbraio 2012
Cristina MasiniAzienda Ospedaliero Universitaria Policlinico di Modena
E.M., ♂, 73 years old
June 2008
• Lumbar pain, not responsive to common anti -inflammatory drugs
• Absence of other symptoms
• Spinal RX: fracture of L2, invisible right pedicle
What would you do now?
1. Lumbar CT scan 1. Lumbar MRI2. Bone scan3. All of the above
CT scanOsteolytic lesion of L2
1
STIR sequence
2
Non-enhanced T1
Lumbar MRI
Osteolysis of L1-L2Newly formed tissue that compresses the dural sac
CT staging with contrast
Chest and abdomen CT:
• Mass in left kidney (9 x 7 cm)
• Multiple lymph adenopathies
Bone scan
L2 lesion
What would you do now?Goal: quality of life
1. Bone biopsy Radiotherapy2. Bone biopsy and vertebroplasty3. Embolization spinal decompression and
stabilization4. Kidney biopsy systemic therapy5. Best supportive care
July 2008Embolization of spinal
pathological vascular bed (L1-L2)
Decompressive laminectomy and stabilization
Histology of L2 lesion: clear cell carcinoma
Radiotherapy D11-L4
What would you do now?
1. Systemic therapy2. Left nephrectomy3. Left nephrectomy systemic therapy4. Best supportive care5. Other
Motzer score: intermediate risk
August 2008
Clear cell carcinoma
Fuhrman nuclear grading system: G2
pT2a, Nx
Left nephrectomy
Retrospective analysis 60 pts with solitary bone metastasis:33 pts had surgical treatment (13 wide resection, 20 local stabilization)27 pts had no surgical treatment
33 pts with bone lesion of axial skeleton 27 pts with bone lesion of appendicular skeleton
Fuchs B., Clin Orthop & related Res 2005
Solitary Bone Metastasis from Renal Cell Carcinoma
October 2008
Start Sunitinib 50 mg daily for 4/2 weeks Zoledronic acid 4 mg every 4 weeks
Lumbar CT:
Spinal stabilization
L1-L2 extensive osteolysis
Chest and abdomen CT:
appearance of bilateral lung lesions
1) Hypertension 170/100 mm Hg (G2)
Good control of blood pressure: 140/80 mm Hg
2) HFSR G2
Start Ramipril 10 mg dailyStart Ramipril 10 mg daily Continue Sunitinib 50 mg daily (4/2)Continue Sunitinib 50 mg daily (4/2)
January 2009...after 3 months of Sunitinib
Ecocardiography: EF 45% (G2)
Asymptomatic patient
Normal ECG
Chest rx: negative
Start Potassium Canrenoate 100 mg daily, bisoprolol 1.25 mg dailyStart Potassium Canrenoate 100 mg daily, bisoprolol 1.25 mg dailyReduced dose of Sunitinib: 37.5 mg daily (4/2)Reduced dose of Sunitinib: 37.5 mg daily (4/2)
April 2009...after 6 months of Sunitinib
May 2009……..after 1 month
Asymptomatic patient
Ecocardiography: EF 55%
Sunitinib 37.5 mg daily (4/2)Bisoprolol 2.5 mg daily and potassium canrenoate 100 mg daily
Chest and abdomen CT:Right pleural effusion and appearance of adrenal mass (3 cm)
Pleural fluid citology: neoplastic cells
Ecocardiography: EF 55%
October 2010...after 24 months of Sunitinib
Progression disease
1. Sorafenib2. Continue Sunitinib3. Everolimus4. Best supportive care
What would you do now?
Which is the optimal sequential treatment?
No response Intolerance Short term benefit
Long term benefit
Porta C, et al. EJMCO 2010Eisen T, modified
TKIs
Stenner F, et al. Oncology (submitted).
Sequencing TKIs: no cross-resistance
1. Eladi R, et al. (manuscript in preparation); 2. Porta C, et al. BJU Int 2011 (Editorial in press)
This is probably due by the fact that in RCC is so heavily dependant on angiogenesis, inhibiting mTOR ultimately results in a continuous, even though indirect, inhibition of angiogenesis2
The issues of long responders….
November 2010
Start Sorafenib 800 mg daily Continue Zoledronic acid 4 mg every 3 months
January 2011...after 2 months of Sorafenib
HFSR (G2)
Stop Sorafenib for 7 days HFSR G1 Restart Sorafenib 800 mg daily
Chest and abdomen CT:Increase of pleural effusion, adrenal mass (4 cm), appearance of liver lesion
August 2011...after 9 months of Sorafenib
Progression disease: STOP SORAFENIB
1. Rechallenge Sunitinib2. Everolimus3. Best supportive care4. Pazopanib
What would you do now?
HR n p EVE PLAC
Everolimus was as effective after 2 Tkis as it was after 1 TKi
Hazard Ratio
Motzer RJ, Cancer 2010Hutson TE, EJC 2009, abs
Median PFS, mos
September 2011
Start Everolimus 10 mg daily Continue Zoledronic acid 4 mg every 3 months
January 2012...after 4 months of Everolimus
Page: 23 of 177Page: 23 of 177 I M: 23 SE: 2I M: 23 SE: 2Compressed 8: 1Compressed 8: 1
cm cm
Chest and abdomen CT:Reduction of pleural effusion, unchanged liver and adrenal masses
SD ongoing Everolimus