Transcript Advanced Ovarian Cancer

Advanced Ovarian Cancer
Introduction
 Ms K 46F
 Recurrent, advanced ovarian cancer
 C4 Chemotherapy
 Paclitaxel/Cisplatin with Avastin (Bevicizumab)
 Hx of significant chemo toxicity
HOPC
 Diagnosed in Oct ‘13
 TAH and SBO for massive ovarian masses
 GP presentation with palpable abdominal masses (Sept ‘13)
 Irregular period
 Fatigue
 Generalised abdominal discomfort and bloating
 Weight loss of 10kg
 Denies nausea and vomiting, change in bowel habits, blood in
stools, thigh pain
HOPC
 U/S revealed large ovarian masses
 Size of “grapefruits”
 Referral to A/Prof Thomas Jobling
 Radical debulking surgery Oct ’13
 Histopathology
 Pathological staging
 Nil radiological assessment
 Significant pain post-operatively, otherwise well
Management
 Referral to A/Prof Gary Richardson Nov ’13
 Chemotherapy (Paclitaxel/Carboplatin)
 Significant toxicity
 Nausea, no vomiting
 Peripheral neuropathy
 Calf cramps
 Generalised arthralgia and myalgia
 Alopecia
 Poor sleep and headache with fatigue
 Anorexia 2° to altered taste sensation
 GORD
 Neutropenia (Lowest of WCC 2.1 and Neutrophils 0.6)
Management
 End of treatment Aug ‘14
 Good progress
 CA-125 consistently down-trending (from 1130 to normal)
 For follow-up with A/Prof Thomas Jobling in six weeks
Recurrence
 Four weeks post-chemotherapy
 Left-sided abdominal pain
 Early follow-up
 CA-125 rose to 231
 Whole body FDG PET/CT scan
 Extensive metastatic disease involving right internal mammary
lymph nodes, capsular surface of liver, and lymph nodes of right
hepatic lobe
Management
 Recommenced chemotherapy on Gemcitabine/Carboplatin
with Avastin
 Difficult to tolerate, increased toxicity
 Allergic reactions x2 (after C2)
 Peripheral neuropathy and facial erythema/swelling
 Managed with anti-histamine and cessation of chemotherapy
 Ceased regimen after C2
Management
 Change to Paclitaxel/Cisplatin with Avastin
 Modest progress (CA-125 from 354 to 200s)
 Well-tolerated
 Currently C2
Past medical history
 Otherwise healthy
 No active issues
 Past history of iron deficiency
 Nil family history of cancers
 Nil history of smoking or alcohol abuse
Social history
 Lives at home with son
 Previously IADL
 Gym 3-4 times weekly
 Currently IpADL
 Attempting daily walks
 Requiring assistances with ADL due to fatigue
 Wide circle of support
Summary
 Ms K 46F
 C2 of paclitaxel/cisplatin with Avastin for recurrence of
advanced ovarian cancer
 Previously on gemcitabine/carboplatin, ceased for allergic
reaction
 Diagnosed with advanced ovarian cancer in Oct ’13 from
TAH/BSO after findings of large ovarian masses
Issues
1.
Recurrent, advanced ovarian cancer

Considerations for Olaparib
2.
Chemotherapy toxicity
3.
Exercise physiologist review
Olaparib and
Ovarian Cancer
Introduction
 Monotherapy in patients with deleterious germ-line BRCA-
mutated, advanced ovarian cancer
 Treated with three or more prior lines of chemotherapy
Mechanisms of action
 Poly ADP-ribose polymerase (PARP) inhibitor
 PARP involved in normal cellular homeostasis (DNA
transcription, cell cycle regulation and DNA repair)
 Inhibit growth of select tumour cell lines, and decreased
tumour growth
 Increased cytotoxicity and anti-tumour activity in cell lines
and tumour models with BRCA mutations
Dosing
 400mg BD PO
 Dose reduction to 200mg BD then 100mg BD in those
experiencing adverse events
Adverse events
 MDS/AML
 Randomised placebo-controlled trial reported 22 of 2,618 (<1%)
patients, 17/22 were fatal
 Recommendation for baseline FBE, and monthly monitoring
 Recommendation for complete recovery from haematological
toxicity prior to commencing Olaparib
 Pneumonitis
 <1% of patient have new or worsening respiratory symptoms
 Embryo-foetal toxicity
 Others
Drug interaction
 CYP3A
 Increase plasma concentration
 Anti-fungal
 Anti-viral
 Anti-retroviral
 Some antibiotics
 Verapramil
 Decrease plasma concentration
 Phenytoin, rifampicin, carbamazepine, and St John’s Wort
Avastin and
Ovarian Cancer
Introduction
 Approved in 2014 by FDA for combination therapy
 For recurrent, advanced ovarian cancer
 Clinical trials revealed
 Decreased rate of recurrences
 Significant improvement in progression-free survival
 Does not increase overall survival rate
Mechanism of action
 Monoclonal antibody
 Anti-angiogenic agent
 Binds vascular endothelial growth factors
 Inhibits tumour progression via
 Slowing or inhibiting tumour growth by restricting neo-
angiogenesis
 Increasing chemotherapeutic efficacy by stabilising tumour blood
vessels
Adverse events
 Infusion reaction
 Impaired wound healing
 Increased risk of bleeding and thromboembolic events
 Increased risk of CCF
 Hypertension
 Proteinura
 Rarely, gastric perforation and formation of fistula or abscess
 Rarely, reversible posterior leukoencephalopathy syndrome
Drug interactions
 Anthracycline
 Combined risk of CCF
 Carboplatin and paclitaxel
 Reduced half-life
 Any drugs that interfere with clotting