onw01 12 therapeutics - solid tumours - case studies

8/2/2019 ONW01 12 Therapeutics - Solid Tumours - Case Studies

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PHCY 471 2012Module 1 Workshop 1

Case Studies

School of Pharmacy, University of OtagoPHCY 471: QUALITY USE OF MEDICINES B

Module 1: Oncology & the Immuno-compromisedWorkshop 1: Therapeutics - Solid Tumours

Case 1

Sally, a 37 year old female, went to her GP after finding a painless lump in her breast.She is worried that she may have breast cancer as her mother died at the age of 50 of breast cancer and her sister received chemotherapy for breast cancer when she was 45years old. Sally has never been pregnant and she started menstruating when she was 10.Sally has also been receiving carbimazole for the last 10 months.Her GPs examination confirmed the presence of a 3.0 cm mass in the upper, outer quadrant of her breast and referred her to the local breast clinic for further investigations.A fine-needle aspirate of the lump showed malignant cells.A partial mastectomy and axillary lymph node dissection was performed. The tumourwas shown to be oestrogen receptor negative and two of the lymph nodes were found tocontain tumour cells. Sallys oncologist recommended that she should receive localradiotherapy to her primary site and axilla in conjunction with six cycles of chemotherapy with 5-flurouracil, epirubicin, and cyclophosphamide (FEC).

1. Does Sally have any risk factors for breast cancer?

Strong Family history (both mother and sister) Early menarchy (increased exposure to estrogen) No pregnancies (increased exposure to estrogen) Female Increasing age (but is a bit early)

But NOT carbimazole

2. Why did Sally s oncologist recommend that she should receive chemotherapy inaddition to surgery and radiotherapy?

Because she is graded at stage II due to invasion of lymph nodes. Therefore, thechemotherapy should stop any micrometastasis.

o Plus is estrogen receptor negative (so theres no hormone therapy added toher treatments)

This improves survival in these people

3. Discuss the mode of action and side effects of the chemotherapy drugs chosen.

5-flurouracil Antimetabolite S-phase specific


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Case Studies

Targets DNA reproduction (pyridine analogue), as it is incorporated into the DNAto stop any further extension of the chain due to the fluorine atom attached.

Side effectso Myelosupporession (watch for bleeding and sore throat and fever, painful

urination)o Mucositis (watch for diarrhoea)o Dermatitiso Diarrhoea

Epirubicin Anthracycline Is not cell cycle specific, which is important Intercalates between the base pairs of DNA, preventing normal function as

enzymes cant work on it properly o Results in DNA cleavage by topoisomerase II and apoptosis

Also generates free radicals, h owever thats a side effect which needs to bemitigated. Side effects (common)

o Alopeciao Diarrhea, nausea and vomitingo Amenorrheao Fever and infectious disease (myelosupproession)

Cyclophosphamide Alkylating agent Also not cell cycle specific Alkylates to binds to nucleophiles, especially DNA to either alkylate or cross link

DNA to prevent normal functiono May lead to apoptosis

Side effectso Nausea and vomitingo Alopeciao Bone marrow suppressiono Hemorrhagic cystitis (due to acrolein)

Administer with Mesna (reduces acrolein)

Generalised ve drug specific reactions (read here for clearer side effects) Generallised

o Nausea and vomiting (hits the chemo trigger zone in the blood brainbarrier)

o Mucocytosis and diarrhoeao Myelocytosis/neutropeniao Hair loss and alopecia

Drug specifico Cardiomyopathy for anthrocyclineso Haemorragic cystitis for cyclophosphamide


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Counter with fluid intake and Mesna

Immediate vs delayed reactions Immediate is within about 30 mins of infusion via central catheter

o Extravasationo

Nausea and vomiting

o Haemorrahic cystisis Delayed

o Diarrhoeao Mouth ulcers/ mucocytosiso Myelosuppression/neutropeniao Hair loss/alopeciao Ovary failureo Myocarditis is accumalative

4. How can these side effects be prevented or minimised?

Antiemetics (H1 or antagonists like ranitidine; metoclopramide or ondansetron,serotonin antagonist plus dexamethasone.)

Pain medication Diarrhoea- loperamide Mesna for cyclophosphamide Mouth ulcers with Bonjela or other oral formulations

o Or just good oral hygene Myelosuppression

o NDIA? is when the neutrophils are at their lowest 7-14 days after chemoo Weekly blood tests to look for thiso And look for specific symptoms NO FEVER

Sore throat Pain on urination etc

o If neutrophils are very low, they are put into isolationo Good oral care (soft toothbrush) and antifungal (nystatin) required.o Stimulate growth of bone marrow

gCSF (granulocyte colony-stimulating factor)- filgastrim causesthem to stimulate more neutrophils

Alopeciao Nope. Just wigs and scarves

5. Could Sally have received treatment with tamoxifen instead of FEC?

No, tamoxifen is an estrogen receptor antagonist. Normally its used to block the estrogenreceptor to prevent growth of the tumour. However, in this case, her cancer cells do nothave the receptor, so theres no point to blocking the rec eptor.


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Three years after receiving adjuvant chemotherapy, Sally began experiencing back painthat was partially relieved by diclofenac 50 mg tds. Sally did not initially go to see herDoctor about the back pain as she thought the pain was due to a pulled muscle caused bymoving furniture in her living room. A week after developing the pain Sally went for aroutine check up at the hospital and mentioned that she had been suffering from back

pain and was now no longer getting any pain relief from diclofenac. A CT scan wasperformed and this revealed the presence of metastases in the spine and right shoulder.

NOTE: lung, liver, brain and bone are the common sites for metastatis

6. What treatment options are now available to Sally for her metastatic breast cancer?

ChemotherapyAnthrocycline

Doxoribicin- NOT a good idea (cumulative toxicity)

Use taxanes Antimitotic agent Paclitaxel Microtubule active drug

7. What pain relief would you recommend for Sally? Include in your answerconsideration of side effects of your recommended treatment and how these can betreated or prevented.

Morphine (long acting), need to give a laxative, a stool softener may be required.

Plus some extra for breaththrough pain, which can be immediate acting morphine as well.

Continuing a NSAID like diclofenac might be a good idea for bone pain.

Bisphosphonate for bone pain e.g. pamidronate


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Case Study 2

Pierce is a 66 year old retired lecturer who was diagnosed with prostate cancer 4 yearsago following routine screening when his PSA was found to be 10 ng/ml and a digitalrectal examination (DRE) revealed a lump that involved more than half of the prostate

gland but was totally enclosed within the gland. The TNM stage of his cancer atdiagnosis was T2bN0M0. He received a course of external beam radiotherapy and histumour shrunk and PSA reduced to normal levels. PSA levels have been checked every 6months since he stopped treatment and he had been undergoing an annual DRE. His PSAis now 20 ng/ml and a transrectal ultrasound scan demonstrated the presence of a tumourinvolving both lobes of the prostate gland that had broken through the capsule of theprostate gland. Bone scan and CT scan showed that the cancer had spread to one lymphnode (< 2 cm in diameter) but had not metastasised. As Pierce is not a candidate forsurgical treatment of his prostate cancer he is prescribed a course of hormonal therapywith goserelin injection 3.6 mg every month and flutamide 250mg 3 times a day for 3weeks.

Pierce has a history of ischaemic heart disease.1. Discuss the tests used to diagnose and monitor Pierce s prostate cancer.

PSA testing- tests for prostate specific antigen, which may be released in greater amountsdue to a tumour. However, it has relatively poor diagnostic specificity. Inflammation of the prostate can also cause a false positive.

DRE- Relatively good diagnostic specificity, allowing the detection of a tumour.However, it is invasive and has a low compliance.

Transrectal ultrasound- Allows basic imaging of the region, can identify points of interestand perform a needle based biopsy.

Bone scan- measured bone density

CT scan- Good resolution, allows for the detection of solid lumps within the body

2. Was the treatment that Pierce initially received appropriate?

Watching and waiting is not a good ideaSurgery is a good idea as its still isolated within the prostate But both the radiation and surgery are fine, so it was appropriate. (Note: brachytherapynot tested here, not recommended, so use the external beam therapy)

3. What is the current TNM classification of Pierce s tumour?

T3N1M0


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4. Discuss the treatment (including adverse effects) that Pierce was prescribed for hisadvanced prostate cancer.

goserelin injection 3.6 mg every month Temporary increase in symptoms and bone painfor the first few weeks (tumour flare), hot flushes, headaches, breast tenderness and

decreased libido.flutamide 250mg 3 times a day for 3 weeks. Bone loss, plus the above.

Groserelin is a LHRH agonist- causes the flareup because it takes some time for thereceptors in the pituitary to become desensitised.Flutamide is a non-steroidal testosterone receptor antagonist, mainly to counter theeffects of the goserelin tumour flare. Therefore, it is only used short term.

Hypothalamus LHRH-> Pituitary LH/FSH-> Testes testosterone-> Prostate

Can also attempt orchidectomy

5. If Pierce s prostate cancer does not respond to his latest treatment what treatmentoptions will be available to him

Wont be the anthrocyclines because hes got ischemic heart disease But chemo therapy in general isnt good in general because they tend to be quite resistant. Radiation isnt appropriate as well, as the tumour has returned within 6 months of radiation therapyDiphosphonates if metastisized into the boneSurgery wont work now, because its metastasized to the local lymph nodes

Therefore, need to focus on palitative care

Note: there are two radiation therapies:

Brachytherapy- implanting radioactive materials into the prostate compared to a beam.

External beam therapy- firing beams of radiation into the prostate.


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Case Study 3

Donald, a Southland farmer, visits a community pharmacy and asks if he can buy

something for his constipation. He says that he started having constipation a few weeks

ago and has been having pains in the gut (abdominal cramps) and bloating. He thinks hemight have lost some weight recently. He also says that his stools have become much

darker this week and he has seen the occasional red stain on the toilet paper after wiping

his bottom. The pharmacist suspects that he might be suffering from a major illness and

recommends that he sees his GP as soon as he can.

Discuss this case using the headings Problems, Options, Plans.

Problems

Constipated for a few weeks Abdominal pain and cramps Bloating Weight loss (alarm sign) Darkened stool with occasional red stain i.e. malaena (alarm sign)

Most likely bowel cancer, due to long term constipation, abdominal pain. Weight loss isanother major symptom, along with the darkened stool and red stain which suggestsabdominal bleeding.

Options

Colonoscopy to check (but hard to do in Dunedin)DRE to check if haemarroids are to blameBarium enema (most likely to use)

Followed by staging

Early (Stage I-III) Surgery to excise tumours (if encapsulated without metastasis)- important

o Needs to go for either a T 3 or T 2 o Need to remove the tumour itself and a few lymph nodes and tissues

around the region. Colostomy (the two ends are separated, one end is facing out into

the world. This allows healing BEFORE joining them together) Radiation therapy (not very effective) Adjuvant therapy with:

o Radiation (at slightly later stages to remove more)


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Not suitable, only good for rectalo Chemo (effective)

FOLFOX- 5-FU, folonic acid Plus oxaliplatin or irinotecan (expensive and side effects,

use for stage 4, but not really for adjucant)

5-FU with leucovorin and oxaliplatin Capecitabine if poor response (prodrug of 5-FU)- probably Biological

o Bevacizumab Nutrition

o Reverse weight loss Cure can be achieved

Late Chemo (as above) Surgery is to only relieve the symptoms

Palliative instead of cure

In addition Pain medication may be required Antiemetics Antifungal creams and mouthwash

Plans

Carry out tests to confirm diagnosis and determine stage

Attempt surgery, use capecitabine or FOLFOX as adjuvant therapy (three weeksafter chemo)

o Chemo can be usually carried out as an outpatient monthly for FOLFOXo Caprecitabine requires dosing by BSA, but given orally. Need to monitor

BSA to make sure. Refer to dietician to reverse weight loss In addition, if chemotherapy is given, give:

o Antiemetics (ondesartan and desomethasone)o Antifungals

Weekly blood tests in case of myleosuppression

Councelling How to use the pumps, and stop if pain occurs (extravascation) Know the symptoms of myelosuppression

onw01 12 therapeutics - solid tumours - case studies

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