Soft Tissue Sarcoma Flashcards
Treatment -Pazopanib Adverse effects -6
VIDEO**
Fatigue,
diarrhea,
nausea,
weight-loss,
hypertension.
Black boxed warning for hepatotoxicity.
Treatment -Pazopanib in advanced STS -6
FDA APPROVED
1ST to show efficacy in non-GIST STS
Advanced STS who have received prior chemotherapy.
TKI
Best in leiomyosarcoma
PFS 4.6 months versus 1.6 months
No significant increase in OS
Not recommended for liposarcoma (ADIPOCYTE)
Treatment – Surgery -4
Cornerstone of therapy.
Goal to achieve cure, avoidance of local recurrence, maximize function and minimize morbidity
Achieve 2 cm margin in all directions.
Failure to achieve adequate margins equals local recurrence rate between 50 and 90%.
Treatment – radiation -2
Used as adjuvant or neoadjuvant.
Goal decrease the need for radical excision to maintain functionality and decrease cosmetic deformity or as an alternative to amputation.
Treatment – radiation toxicity -6
Bone tissue damage,
bone fracture,
edema,
fibrosis,
functional impairment,
impaired wound healing.
Treatment – radiation modalities -4
Post operative external beam radiotherapy,
adjuvant Brachytherapy,
intraoperative radiation,
pre-operative external beam radiotherapy
Chemotherapy – neoadjuvant -6
Unclear benefit.
Goal avoid aggressive surgery or amputation.
- Decrease tumor size prior to surgery allowing for less extensive surgery
- treating micro metastatic disease earlier in disease course prior to development of drug resistance
- administering chemotherapy prior to surgery induced damage to the local vasculature surrounding the tumor site
- discerning pathological tumor response to chemotherapy following resection
Chemotherapy – adjuvant Doxorubicin-containing chemo regimen -3
meta-analysis - Improved local and distant recurrence – free survival, overall recurrence – free survival.
meta-analysis - Trend towards improving overall survival but NS, others show inc OS
phase III - no OS benefit, similar recurrence free survival
NO CLEAR DATA - make decision based on patient, location, and type of tumor FOR BOTH NEOADJ AND ADJ
Metastatic disease concepts -6
Half of patients will relapse with disease at a distance site.
Chemotherapy for palliation.
Median survival one year.
Response to chemo is poor about 10 to 20%.
Combination chemotherapy common (inc response) but does NOT increase OS
DOXORUBICIN considered to be most active
Metastatic disease – factors predicting favorable response -5
Performance status,
lack of hepatic involvement,
low grade histology,
long disease free survival from diagnosis,
age.
Metastatic disease – intra-arterial chemotherapy
No proven benefit over systemic Chemotherapy
optimize drug concentration at tumor site
Metastatic disease – chemotherapy choices -7
Doxorubicin 75mg/m2– RR – 20%. PLD 50mg/m2 Ifosfamide – 15 to 20% dacarbazine – 15 to 20% Cisplatin – 15% Epirubicin 75– 15% cyclophosphamide – 10% actinomycin D – 15%
Metastatic disease – limb perfusion therapy - what is it? toxicity? -5
use of tourniquet to isolate blood flow in area of tumor
Melphalan + tumor necrosis factor.
No data to assess efficacy!! no comparison with systemic tx
Toxicity:
Functional impairment from local tissue and muscle damage,
Edema,
thromboembolic disease.
Metastatic disease – Doxil versus doxorubicin -3
Same response rate but different toxicities.
Doxil: Palmer – planter erythrodyesethesia 50% vs 0% for doxo.
Doxorubicin: Grade 3/4 neutropenia 77%, Doxil 6%
Kaposi’s sarcoma - Treatment options -6
Lots of treatment options.
Local: Radiotherapy – 85% CR.
Surgery – 56% with no recurrence after resection.
Systemic: HAART – 22%.
Oral etoposide 74%.
PLD
Kaposi’s sarcoma - background -4
Mostly seen in patients with AIDS
a low grade vascular tumor
associated with human herpes virus 8
has been treated with radiation, surgery and chemo
soft tissue sarcoma - tissues involved -6
fat
muscle
nerve and nerve sheath
blood vessels
cartilage
other connective tissue
soft tissue sarcoma - types -6
leiomyosarcoma
malignant fibrous histiocytoma
liposarcoma
dermatofibrosarcoma
rhabdomyosarcoma
angiosarcoma
soft tissue sarcoma - staging -4
Tumor size
lymph node involvement
metastasis
grade (well differentiated vs poorly differentiated)
Gastrointestinal stromal tumors (GIST) - imatinib - MOA and concepts -5
poorly responsive to chemo and radiation, previous SOC was surgery
c-kit gene is activated in 85-90% of GIST cases, PDGF: 5% of GIST cases
inhibits c-kit
Continue imatinib until the disease progresses
Primary resistance to imatinib develops in about 20% of patients
Gastrointestinal stromal tumors (GIST) - regorafenib -4
Improved PFS in patients who had previously failed imatinib and sunitinib
blocks c-kit, other kinases
160mg daily 3wks ON, 1wk OFF
PFS 4.8 vs 0.9mo
regorafenib - adverse effects -4
hypertension,
hand-foot syndrome,
diarrhea,
rash or desquamation
screening - STS -1
NONE
most common mets site -1
2/3 lung
is chemo well defined for sarcoma?
NO
ONLY for rhabdomyosarcoma, osteo, Ewing’s
combo regimens for mets dz -7
ALL CYCLES 21-28 DAYS
AI: doxo, ifos, mesna
MAID: mesna, doxo, ifos, dacarb
CyVADIC: doxo, dacarb, yc, vincristine
gem-doce (shows response post doxo tx)
gem-vinorelbine
ifos 6-14G/M2
temozolomide
Gastrointestinal stromal tumors (GIST) - if fail imatinib
sunitinib
TTP 6.3 vs 1.5mo
sunitinib MOA and dose
VEGF, PDGFR, c-kit, Flt-3
antitumor, antiangiogenic
50 daily 4wks on, 2 wks off
sunitinib ADR
fatigue
D, N
sore mouth
HFS
HTN
neutrop, anemia, thrombocytop
desmoid tumor tx
tamoxifen
sulindac (other NSAIDs)
MTX
vinblastine
mesothelioma tumor tx
only cure surgery
advanced, dz: cisplatin + pemetrexed
in adults is STS or bone sarcoma more common?
STS
Does histology drive treatment?
YES
Unresectable and/or metastatic GIST
OR
Preoperative imatinib for GIST that is resectable with negative margins but with risk of significant morbidity
Starting imatinib
Initiate dosing at 400 mg daily.
Patients with documented mutations in KIT exon 9 may benefit from dose escalation up to 800 mg daily (given as 400 mg twice daily), depending upon tolerance.
IF PROGRESSION OF DISEASE IS DOCUMENTED: Imatinib dose increase up to 800 mg daily (given as 400 mg twice daily) may be considered, as clinically tolerated, in patients showing objective signs of disease progression at a lower dose and in the absence of severe adverse drug reactions.
Postoperative imatinib - starting dose
400 mg daily following complete gross resection of GIST.
Imatinib should be taken with a low-fat meal and a large glass of water
% of patients respond to imatinib when their tumors have a KIT exon 11 mutation
90
% of patients respond to imatinib when their tumors have a KIT exon 9 mutation
50
can increase to 400mg bid
