Treatment Journey of Mr. R: Adenocarcinoma Case Study

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Laura Bidstrup
Mr R attended for review and maintenance
therapy for adenocarcinoma of unknown
primary
Apr 2011: 
attended GP regarding ~2 days severe
sharp pain from RLQ to shoulder; US/CT = liver
lesions. Bx = met adenocarcinoma. Commenced on
Cisplatin/Gemcitabine.
May 2011: 
Pain continuing (dull ache, RUQ/shoulder).
Markers decreasing, nil SEs
Jun 2011: 
ECOG 2, nil SEs
. 
Splenic met found on CT,
markers increasing; not responding to Cis/Gem
Jul 2011: 
Commenced Folfiri-m/beva. Mild GIT
toxicity/lightheadedness for 2/7. ECOG 0.
Swelling/tender in R) arm- subclav/axillary DVT.
(
Clexane).
Aug 2011: 
Dec met size on CT, dec markers. Nil SEs.
Sep 2011: 
ECOG 0. Some mucositis, resolved with dec
dose.
Oct 2011: 
~ inc markers. Dec met size. ECOG 0.
Nov 2011: 
Mild gen abdo pain/diarrhoea. ECOG 1.
Dec 2011: 
Dec met size. Commenced maintenance
Bev/cape. Tiredness, dec short term memory and
concentration, ~diarrhoea. 
Jan-Apr 2012: 
ECOG 1. Nil sig SEs. Dec markers.
Occasional mild R) shoulder/costal margin pain.
Exam normal.
May-Jun 2012: 
R) shoulder/CM pain resolved w/
Dex. Markers ~ increasing.
Jul 2012: 
Lower back pain
headache. Fatigue, nil
other sx (esp neuro)
Aug-Sep 2012: 
Mets unchanged on Ix, nil issues.
Oct 2012: 
~appetite, ECOG 1, dose reduced due to
minor mucositis, nausea, changed bowel habit
Dec 2012-Mar 2013: 
RUQ pain controlled w/ panadeine
forte. ECOG 1, Grade 1 Hand/foot, other SEs settled
Apr 2013: 
 Pain
 severe. Reactions to opioids. Ref to
pall med. Sig disease progression on CT, lesions
markedly larger. Markers x2 in 3/52.Commenced
Folfoxiri/Bev.
May 2013: 
Markers dec by 50%. SEs: grade 1
diarrhoea/nausea/cramps/periph neuro. ECOG 1.
Jun 2013: 
CT stable, but deteriorating condition.
Commenced Carboplat/pacli/bev/cape.
Jul 2013: 
Dec markers. Severe abdo pain ~2-3/7 after
C1, required endone
Sep 2013
: Feb neutropaenia (Admit x5/7, Abx).
Numbness over distal ½ feet. ~5/7 myalgia.
Oct-Nov 2013
: ECOG 1-2. Stable periph neuro. LL
wasting. Nil change on CT. Dec markers.
Dec 2013:
 feb neutropaenia (admit x 4/7, IV abx. ?LRTI)
Jan-May 2014: 
pain controlled, ECOG 1, stable.
Current medications: Endone, Ativan, Dex,
meloxicam, nexium, Mg2+, durogesic 25mcg
Phx
Allergies: erythromycin (?reactions to opioids)
Migraines
Nil other hx
FHx
Mother: breast ca ages 66/72. Alive and doing well.
Grandfather: Met skin cancer, died in 70s
Nil other known
Social
Mr R lives with his wife and three children. Eldest
child lives out of home and has 2 children.
Self employed motorcycle restorer; previously w/
large company. Nil financial issues.
Smoking hx: never smoked
Alcohol: ~ binge monthly before dx
Initial Dx: Adenocarcinoma of unknown
primary
RX (earliest
most recent)
:
1.
3x Cisplatin/Gemcitabine
2.
12x Folfiri m/ beva
3.
3x Beva/cape
4.
5x Folfoxiri/beva
5.
15x Carboplatin/Paclitaxel/beva/cape
Additional medications
Hydrocortisone
Phenergan
Aprepitant (CINV)
Palonsteron (CINV)
NaCl (hydration)
undefined
 
 
Incidence:
8
th
 most common cancer in men, 9
th
 in
women
6
th
 most common cause of cancer death in
Australians (around 5% of cancer deaths)
2009: ~2900 people in Australia were
diagnosed with CUP.
Mortality
: 
In 2007, there were 2344 CUP-
related deaths
Aetiology:
Unknown?
Pathophys
Normally, mets appear like abnormal versions of the primary; if not
identifiable= CUP
Attributes of CUP: Early dissemination, clinical absence of primary tumour,
unpredictable metastatic pattern, and aggressiveness
Four major subtypes:
Adenocarcinomas (well to moderately differentiated)
Poorly differentiated carcinomas and adenocarcinomas
Squamous cell carcinomas
Undifferentiated neoplasms
Majority of cases are adenocarcinomas, then poorly differentiated tumours
Main hypothesis: primary tumour remains microscopic, thus evading
detection by available techniques; or disappears completely after seeding
the metastasis
Stage:
Likely IV, ?III/II
Risk Factors
Smoking, older age, poor diet, alcohol and obesity
Depends on the predominant site of
metastatic involvement.
Often asymptomatic
Typical ca sx;
SOB/chest discomfort
Bone/back pain
Ascites, abdo discomfort, jaundice
Lymphadenopathy
Weight loss
Headaches
Anorexia
Fatigue
Ix
Clinical exam
FOBT
Bloods (FBE, UEC, LFT,CEA)
Urinalysis
Bx
CT/PET/MRI
Ddx
Squamous or neuroendocrine
carcinoma of unknown primary
Met of known primary
Prognosis:
Not diagnosed until metastatic disease
Treatment difficult due to unknown primary cancer
type
Five year survival:16%.
Median survival: 3 to 4 months, up to 6 to 11
months with combination chemotherapy in selected
populations.
Factors
Site, general health
Potentially curable in favourable circumstances
Supportive
RT only in certain localised cases
Chemo:
Almost every class of cytotoxic chemotherapeutic
agent has been assessed. Response rates are low;
however modern combo regimens more effective
Should either be treated on trial basis with
proposed future regimens, or low-toxicity
(palliative/maintenance) treatment
undefined
SE:
Caution: neutropaenic sepsis
(admit)
Immediate (onset hours to
days)
Cardiotoxicity a/w
Capecitabine
N/V
Taste change
Hypersensitivity reaction
Early (onset days to weeks)
Anaemia/neutropenia/thrombo
cytopenia (delay)
Oral mucositis 
Hand-foot syndrome
Fatigue
Arthralgia/myalgia
Diarrhoea
Hyperlacrimation
Actinic keratoses flare
HTN
Proteinuria
Photosensitivity
Gastric perforation
Thromboembolism
Expstaxis
Late (onset weeks to
months)
Alopecia
Nail changes
Hyperpigmentation
Hyperbilirubinaemia
Cognitive changes
 
Carboplatin/Paclitaxel/Bevacizumab/Capecitabine
Repeated every 4-6 weeks
Platinum/taxane combinations are widely used;
yielding response rates of 30% and median overall
survival of 9–11 months in certain CUP patients.
A ‘gold standard' of therapy for adenocarcinoma or
poorly differentiated CUP site has not been found
Efficacy of any chemotherapy for CUP is relatively low
(most die within 2 years) 
 
need for an optimisation
of treatment, eg by better characterisation of the
tumour, or of markers for predicting response
A recent pilot study combining bevacizumab and
erlotinib showed considerable efficacy; median
overall survival of 7.4 months and 33% of patients
alive at 1 year.
Paclitaxel/carboplatin (arm A) or the non-platinum non-
taxane regimen gemcitabine/vinorelbine (arm B)
EviQ
Best Practice
Australian Cancer Council
Manual of Clinical Oncology, seventh ed.
1.
Briasoulis, E. and N. Pavlidis. 1997. "Cancer of Unknown
Primary Origin." Oncologist 2(3):142-152.
2.
Briasoulis, E., H. Kalofonos, D. Bafaloukos, et al. 2000.
"Carboplatin plus paclitaxel in unknown primary
carcinoma: a phase II Hellenic Cooperative Oncology
Group Study." J.Clin Oncol. 18(17):3101-3107.
3.
Huebner, G., H. Link, C. H. Kohne, et al. 2009. "Paclitaxel
and carboplatin vs gemcitabine and vinorelbine in
patients with adeno- or undifferentiated carcinoma of
unknown primary: a randomised prospective phase II
trial." Br J Cancer 100(1):44-49.
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Mr. R's treatment journey for adenocarcinoma of unknown primary involved various therapies like Cisplatin/Gemcitabine, Folfiri-m/beva, Bev/cape, and Folfoxiri/Bev. He experienced different symptoms and side effects, with disease progression and varying responses to treatment. The summary encompasses his medical history, treatments, and progress over time.


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  1. Laura Bidstrup

  2. Mr R attended for review and maintenance therapy for adenocarcinoma of unknown primary

  3. Apr 2011: sharp pain from RLQ to shoulder; US/CT = liver lesions. Bx = met adenocarcinoma. Commenced on Cisplatin/Gemcitabine. May 2011: Markers decreasing, nil SEs Jun 2011: markers increasing; not responding to Cis/Gem Jul 2011: toxicity/lightheadedness for 2/7. ECOG 0. Swelling/tender in R) arm- subclav/axillary DVT. ( Clexane). Aug 2011: Sep 2011: dose. Oct 2011: Apr 2011: attended GP regarding ~2 days severe May 2011: Pain continuing (dull ache, RUQ/shoulder). Jun 2011: ECOG 2, nil SEs. . Splenic met found on CT, Jul 2011: Commenced Folfiri-m/beva. Mild GIT Aug 2011: Dec met size on CT, dec markers. Nil SEs. Sep 2011: ECOG 0. Some mucositis, resolved with dec Oct 2011: ~ inc markers. Dec met size. ECOG 0.

  4. Nov 2011: Dec 2011: Bev/cape. Tiredness, dec short term memory and concentration, ~diarrhoea. Jan Occasional mild R) shoulder/costal margin pain. Exam normal. May Dex. Markers ~ increasing. Jul 2012: other sx (esp neuro) Aug Oct 2012: minor mucositis, nausea, changed bowel habit Nov 2011: Mild gen abdo pain/diarrhoea. ECOG 1. Dec 2011: Dec met size. Commenced maintenance Jan- -Apr Apr 2012: 2012: ECOG 1. Nil sig SEs. Dec markers. May- -Jun 2012: Jun 2012: R) shoulder/CM pain resolved w/ Jul 2012: Lower back pain headache. Fatigue, nil Aug- -Sep 2012: Oct 2012: ~appetite, ECOG 1, dose reduced due to Sep 2012: Mets unchanged on Ix, nil issues.

  5. Dec 2012 forte. ECOG 1, Grade 1 Hand/foot, other SEs settled Apr 2013 pall med. Sig disease progression on CT, lesions markedly larger. Markers x2 in 3/52.Commenced Folfoxiri/Bev. May 2013 diarrhoea/nausea/cramps/periph neuro. ECOG 1. Jun 2013 Commenced Carboplat/pacli/bev/cape. Jul 2013: C1, required endone Sep 2013 Numbness over distal feet. ~5/7 myalgia. Oct wasting. Nil change on CT. Dec markers. Dec 2013: Jan Dec 2012- -Mar 2013: Mar 2013: RUQ pain controlled w/ panadeine Apr 2013: : Pain severe. Reactions to opioids. Ref to May 2013: : Markers dec by 50%. SEs: grade 1 Jun 2013: : CT stable, but deteriorating condition. Jul 2013: Dec markers. Severe abdo pain ~2-3/7 after Sep 2013: Feb neutropaenia (Admit x5/7, Abx). Oct- -Nov 2013 Nov 2013: ECOG 1-2. Stable periph neuro. LL Dec 2013: feb neutropaenia (admit x 4/7, IV abx. ?LRTI) Jan- -May 2014: May 2014: pain controlled, ECOG 1, stable.

  6. Current medications: Endone, Ativan, Dex, meloxicam, nexium, Mg2+, durogesic 25mcg Phx Allergies: erythromycin (?reactions to opioids) Migraines Nil other hx FHx Mother: breast ca ages 66/72. Alive and doing well. Grandfather: Met skin cancer, died in 70s Nil other known

  7. Social Mr R lives with his wife and three children. Eldest child lives out of home and has 2 children. Self employed motorcycle restorer; previously w/ large company. Nil financial issues. Smoking hx: never smoked Alcohol: ~ binge monthly before dx

  8. Initial Dx: Adenocarcinoma of unknown primary RX (earliest most recent): 1. 3x Cisplatin/Gemcitabine 2. 12x Folfiri m/ beva 3. 3x Beva/cape 4. 5x Folfoxiri/beva 5. 15x Carboplatin/Paclitaxel/beva/cape Additional medications Hydrocortisone Phenergan Aprepitant (CINV) Palonsteron (CINV) NaCl (hydration)

  9. Incidence: 8thmost common cancer in men, 9thin women 6thmost common cause of cancer death in Australians (around 5% of cancer deaths) 2009: ~2900 people in Australia were diagnosed with CUP. Mortality: In 2007, there were 2344 CUP- related deaths Aetiology: Unknown?

  10. Pathophys Normally, mets appear like abnormal versions of the primary; if not identifiable= CUP Attributes of CUP: Early dissemination, clinical absence of primary tumour, unpredictable metastatic pattern, and aggressiveness Four major subtypes: Adenocarcinomas (well to moderately differentiated) Poorly differentiated carcinomas and adenocarcinomas Squamous cell carcinomas Undifferentiated neoplasms Majority of cases are adenocarcinomas, then poorly differentiated tumours Main hypothesis: primary tumour remains microscopic, thus evading detection by available techniques; or disappears completely after seeding the metastasis Stage: Likely IV, ?III/II Risk Factors Smoking, older age, poor diet, alcohol and obesity

  11. Depends on the predominant site of metastatic involvement. Often asymptomatic Typical ca sx; SOB/chest discomfort Bone/back pain Ascites, abdo discomfort, jaundice Lymphadenopathy Weight loss Headaches Anorexia Fatigue

  12. Ix Clinical exam FOBT Bloods (FBE, UEC, LFT,CEA) Urinalysis Bx CT/PET/MRI Ddx Squamous or neuroendocrine carcinoma of unknown primary Met of known primary

  13. Prognosis: Not diagnosed until metastatic disease Treatment difficult due to unknown primary cancer type Five year survival:16%. Median survival: 3 to 4 months, up to 6 to 11 months with combination chemotherapy in selected populations. Factors Site, general health Potentially curable in favourable circumstances

  14. Supportive RT only in certain localised cases Chemo: Almost every class of cytotoxic chemotherapeutic agent has been assessed. Response rates are low; however modern combo regimens more effective Should either be treated on trial basis with proposed future regimens, or low-toxicity (palliative/maintenance) treatment

  15. Carboplatin/Paclitaxel/ Repeated every 4-6 weeks Carboplatin/Paclitaxel/Bevacizumab Bevacizumab/ /Capecitabine Capecitabine SE: Caution: neutropaenic sepsis (admit) Immediate (onset hours to days) Cardiotoxicity a/w Capecitabine N/V Taste change Hypersensitivity reaction Early (onset days to weeks) Anaemia/neutropenia/thrombo cytopenia (delay) Oral mucositis Hand-foot syndrome Fatigue Arthralgia/myalgia Diarrhoea Hyperlacrimation Actinic keratoses flare HTN Proteinuria Photosensitivity Gastric perforation Thromboembolism Expstaxis Late (onset weeks to months) Alopecia Nail changes Hyperpigmentation Hyperbilirubinaemia Cognitive changes

  16. Platinum/taxane combinations are widely used; yielding response rates of 30% and median overall survival of 9 11 months in certain CUP patients. A gold standard' of therapy for adenocarcinoma or poorly differentiated CUP site has not been found Efficacy of any chemotherapy for CUP is relatively low (most die within 2 years) need for an optimisation of treatment, eg by better characterisation of the tumour, or of markers for predicting response A recent pilot study combining bevacizumab and erlotinib showed considerable efficacy; median overall survival of 7.4 months and 33% of patients alive at 1 year.

  17. Paclitaxel/carboplatin (arm A) or the non-platinum non- taxane regimen gemcitabine/vinorelbine (arm B)

  18. EviQ Best Practice Australian Cancer Council Manual of Clinical Oncology, seventh ed. 1. Briasoulis, E. and N. Pavlidis. 1997. "Cancer of Unknown Primary Origin." Oncologist 2(3):142-152. 2. Briasoulis, E., H. Kalofonos, D. Bafaloukos, et al. 2000. "Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study." J.Clin Oncol. 18(17):3101-3107. 3. Huebner, G., H. Link, C. H. Kohne, et al. 2009. "Paclitaxel and carboplatin vs gemcitabine and vinorelbine in patients with adeno- or undifferentiated carcinoma of unknown primary: a randomised prospective phase II trial." Br J Cancer 100(1):44-49.

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