For stage II and IIIA- get PDL1, EGFR, ALK
If EGFR neg--> NACT platinum doublet with nivo 3 cycles
Adjuvant
If EGFR, ALK neg, and PDL1 0- after adjuvant chemo, pembro
If EGFR positive, after chemo, osimertinib for 3 yr
If EGFR and ALK neg, PDL1 > 50, can consider atezo although pembro would be fine
For ALK mutation positive--> after 4 cycles chemo, no IO. Can consider clinical trial.
All patients with metastatic CSPC should receive ADT, with the addition of other modalities depending on patient-specific factors and the extent of disease. Choices include orchiectomy, Gnrh agonists or antagonists. Gnrh agonists are commonly administered as monthly, 3 month or 6 month injections.
Relugolix is a GNRH antagonist. Compared to ADT it is associated with less major adverse cardiovascular events. This difference is more pronounced in patients with past hx of a major CV event.
Leuprolide and Eligard are the most commonly used ADT meds. These are given intramuscularly.
ADT is associated with metabolic, cardiovascular, musculoskeletal, cognitive, and neuropsychiatric issues, as well as sexual dysfunction.
1. Osteoporosis prevention: Bisphosphonates do not reduce skeletal related events in newly diagnosed castrate sensitive met prostate cancer based on CALGB 90202 study and STAMPEDE trial. However, a baseline DXA scan is indicated to identify underlying osteoporosis or high risk osteopenia which may worsen with ADT. Calcium and vitamin D supplementation are indicated.
Recommended:
DXA scan
Calcium 1000 mg with vit D3 1000 units daily
If DXA shows high risk osteopenia ( T score less than neg 2) or osteoporosis ( T less than neg2.5), then will discuss bisphosphonates q 6 m.
2. Sarcopenia and risk of falls : These are well known side effects. I recommended strength training at least 20 min a day 3 days a week along with stretching exercises.
3. Cardiovascular risk factors: The patients cardiac risk factors were evaluated.
No hx of ongoing angina or exertional dyspnea. Can climb 2 flights of stairs without stopping. No CP at rest. No hx of MI or cardiac stents. Has a hx of controlled hypertension being managed by PCP. Current meds include:
He is on aspirin but not on an anticoagulant.
4. Fatigue is also extremely common with ADT. Exercise can help with this.
Hot flashes and gynecomastia: discussed these side effects. Gabapentin, acupuncture and effexor can help.
5. We will monitor lipid panel annually as well as weight gain since ADT increases risk of metabolic syndrome.
6. Erectile dysfunction is a common side effect.
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Frontline is platinum based chemo with or without bev.
Germline BRCA or HRD, negative-- Observation is ok, Niraparib cat 2A based on PRIMA. Also PRIME trial showed benefit in all comers ( stage III was included, therefore good risk patients). HR 0.72 with a 16 month versus 8 month PFS benefit in HRP versus placebo.
HRD positive BRCA WT PAOLA-1 data
In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation
Germline or somatic BRCA mutations POSITIVE
Niraparib and olaparib are NCCN category 1 recommended options for those with germline or somatic BRCA1/2 mutations who are in complete or partial remission after surgery and platinum-based first-line chemotherapy
Rash lasts the first 6 weeks.
Intensity of rash correlates with efficacy
STEPP trial was the first prospective trial which showed a benefit with 6 weeks of doxycycline or minocycline to prevent grade 2 or higher rash.
CTC criteria using BSA may not apply. Another risk stratification is used specific for EGFR Ab.
Flowchart for grades of toxicity and management
Grade 1 : mild pustular with no other symptoms.
Rx: topical clinda 2% with hydrocortisone 1% apply BID lotion ( although generally speaking refrigerated emollient alcohol free cream is better for the rest of the body).
Grade 2: Moderately symptomatic, moderate pustular with erythema, may or may not interfere with ADL
As with grade 1 + oral doxy until rash resolution+ for scalp lesions clinda with triamcinolone
Grade 3: Moderate to severe intolerable rash, interferes with ADL
"Several situations warrant patient referral to a dermatologist. Clinicians may wish to refer if the skin toxicity does not improve within 1–2 weeks of treatment. Referral is also recommended if the patient is severely symptomatic (for example, if necrosis, blistering, or petechial or purpuric lesions are present) or if multiple hair, nail, and skin issues emerge 29. In general, if the skin toxicity has an uncharacteristic appearance or distribution (it just doesn’t look “right” or familiar), it is advisable to refer the patient to a dermatologist."
IMPEDE or SAVED score can be used.
SAVED score 3 or higher --> use Lovenox 40 mg daily, OR Warfarin INR 2-3, Rivaroxaban 10 mg or Eliquis 2.5 mg BID
Otherwise Aspirin 325 mg or 81 mg
SAVED score
This post will be continuously updated.
1. Constipation
-types of meds: stool softeners ( docusate), stimulant laxatives ( senna), bulking agents ( psyllium), osmotic laxatives ( milk of magnesia, laculose).
For opiate induced constipation--> stimulants may be needed. Softeners and bulking agents do not work on their own.
-conside Lubiprostone for chronic IBS associated constipation.
-naltrexone can reverse opiate constipation.
2. Cancer related fatigue:
Assessment:
Pharmacologic rx: phase II data for methylphenidate. No convincing evidence for modafinil or ginseng.
