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Oxaliplatin 200mg/40ml concentrate for solution for infusion vials | 1 vial P £595.65–£627.00 (Hospital only) | 1 vial P £591.26

ANTINEOPLASTIC DRUGS › PODOPHYLLOTOXIN

DERIVATIVES

Etoposide 12-Jul-2018

l INDICATIONS AND DOSE

Small cell carcinoma of the bronchus, the lymphomas and

testicular cancer

▶ BY MOUTH

▶ Adult: 120–240 mg/m2 daily for 5 days

▶ BY INTRAVENOUS INFUSION

▶ Adult: (consult product literature)

IMPORTANT SAFETY INFORMATION

RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES

See Cytotoxic drugs p. 888.

l INTERACTIONS → Appendix 1: etoposide

l SIDE-EFFECTS

GENERAL SIDE-EFFECTS

▶ Common or very common Abdominal pain . acute

leukaemia . alopecia . anaemia . appetite decreased . arrhythmia . asthenia . bone marrow depression . constipation . diarrhoea . dizziness . hepatotoxicity . hypertension . leucopenia . malaise . mucositis . myocardial

infarction . nausea . neutropenia . skin reactions . thrombocytopenia . vomiting

▶ Uncommon Nerve disorders

▶ Rare or very rare Dysphagia . neurotoxicity .radiation

recall reaction .respiratory disorders . seizure . severe

cutaneous adverse reactions (SCARs).taste altered . vision

loss

SPECIFIC SIDE-EFFECTS

▶ Common or very common

▶ With intravenous use Anaphylactic reaction . hypotension . infection

▶ With oral use Oesophagitis . stomatitis .transient systolic

hypotension

▶ Uncommon

▶ With intravenous use Haemorrhage

▶ Rare or very rare

▶ With intravenous use Fever

▶ With oral use Drowsiness

▶ Frequency not known

▶ With intravenous use Angioedema . extravasation necrosis . infertility .tumour lysis syndrome

l CONCEPTION AND CONTRACEPTION Contraceptive advice

required, see Pregnancy and reproductive function in

Cytotoxic drugs p. 888.

l PREGNANCY Avoid (teratogenic in animal studies). See

also Pregnancy and reproductive function in Cytotoxic drugs

p. 888.

l BREAST FEEDING Discontinue breast-feeding.

l HEPATIC IMPAIRMENT Manufacturer advises caution

(increased risk of accumulation).

l RENAL IMPAIRMENT

Dose adjustments Consider dose reduction—consult local

treatment protocol for details.

l DIRECTIONS FOR ADMINISTRATION Etoposide may be given

orally or by slow intravenous infusion, the oral dose being

double the intravenous dose. A preparation containing

etoposide phosphate can be given by intravenous injection

or infusion. Etoposide is usually given daily for 3–5 days

and courses should not be repeated more frequently than

at intervals of 21 days.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Solution for infusion

▶ Etoposide (Non-proprietary)

Etoposide 20 mg per 1 ml Etoposide 100mg/5ml concentrate for

solution for infusion vials | 1 vial P £11.50–£15.51 (Hospital only)

Etoposide 200mg/10ml concentrate for solution for infusion vials | 1 vial P s (Hospital only)

Etoposide 500mg/25ml concentrate for solution for infusion vials | 1 vial P £60.70–£77.54 (Hospital only)

Capsule

CAUTIONARY AND ADVISORY LABELS 23

▶ Vepesid (Bristol-Myers Squibb Pharmaceuticals Ltd)

Etoposide 50 mg Vepesid 50mg capsules | 20 capsule P £99.82

(Hospital only)

Etoposide 100 mg Vepesid 100mg capsules | 10 capsule P £87.23 (Hospital only)

Powder for solution for injection

▶ Etopophos (Bristol-Myers Squibb Pharmaceuticals Ltd)

Etoposide (as Etoposide phosphate) 100 mg Etopophos 100mg

powder for solution for injection vials | 10 vial P £261.68

(Hospital only)

ANTINEOPLASTIC DRUGS › TAXANES

Cabazitaxel 11-Feb-2019

l INDICATIONS AND DOSE

Treatment of hormone refractory metastatic prostate

cancer in patients who have previously been treated

with a docetaxel-containing regimen (in combination

with prednisone or prednisolone)

▶ BY INTRAVENOUS INFUSION

▶ Adult: (consult product literature or local protocols)

l CAUTIONS Avoid in Acute porphyrias p. 1058

l INTERACTIONS → Appendix 1: taxanes

l SIDE-EFFECTS

▶ Common or very common Acute kidney injury . alopecia . anaemia . anxiety . appetite decreased . arrhythmias . arthralgia . asthenia . chest pain . chills . confusion . conjunctivitis . constipation . cough . cystitis . deep vein

thrombosis . dehydration . diarrhoea . dizziness . dry

mouth . dyspnoea . excessive tearing . fever. gastrointestinal discomfort. gastrointestinal disorders . haemorrhage . headache . hydronephrosis . hyperglycaemia . hypersensitivity . hypertension . hypokalaemia . hypotension . increased risk of infection . lethargy . leucopenia . malaise . mucositis . muscle complaints . nausea . nerve disorders . neutropenia . oedema . oropharyngeal pain . pain . pelvic pain .renal colic .renal

failure (fatal cases of renal failure reported). sensation

abnormal . sepsis . skin reactions .taste altered . thrombocytopenia .tinnitus . ureteral obstruction . urinary

disorders . vasodilation . vertigo . vomiting . weight

decreased

▶ Frequency not known Respiratory disorders

l CONCEPTION AND CONTRACEPTION Ensure effective

contraception during treatment (women) and for up to

6 months after treatment (men).

l PREGNANCY See also Pregnancy and reproductive function

in Cytotoxic drugs p. 888.

l BREAST FEEDING Discontinue breast-feeding.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

mild to moderate impairment; avoid in severe impairment.

Dose adjustments Manufacturer advises dose reduction in

mild to moderate impairment—consult product literature.

l RENAL IMPAIRMENT Use with caution if creatinine

clearance less than 50 mL/minute.

l MONITORING REQUIREMENTS Monitor electrolytes—

correct dehydration.

BNF 78 Cytotoxic responsive malignancy 923

Immune system and malignant disease

8

l DIRECTIONS FOR ADMINISTRATION Intravenous infusion

incompatible with PVC.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Cabazitaxel for hormone-relapsed metastatic prostate cancer

treated with docetaxel (updated August 2016) NICE TA391

Cabazitaxel (Jevtana ®) in combination with prednisone or

prednisolone is recommended as an option for treating

metastatic hormone-relapsed prostate cancer in patients

whose disease has progressed during or after docetaxel

chemotherapy, only if the following criteria are met:

. the patient has an eastern cooperative oncology group

(ECOG) performance status of 0 or 1

. the patient has had 225 mg/m2 or more of docetaxel

. treatment with cabazitaxel is stopped when the disease

progresses or after a maximum of 10 cycles

. the manufacturer provides cabazitaxel with the discount

agreed in the patient access scheme

. NHS trusts purchase cabazitaxel in accordance with the

commercial access agreement, either in vials (at a

reduced price to reflect the average cost of waste per

patient), or in pre-prepared intravenous infusion bags.

Patients currently receiving cabazitaxel that is not

recommended according to the above criteria should have

the option to continue treatment until they and their NHS

clinician consider it appropriate to stop.

www.nice.org.uk/guidance/ta391

Scottish Medicines Consortium (SMC) decisions

SMC No. 735/11

The Scottish Medicines Consortium has advised (December

2016) that cabazitaxel (Jevtana ®) in combination with

prednisone or prednisolone is accepted for restricted use

within NHS Scotland for the treatment of patients with

hormone refractory metastatic prostate cancer previously

treated with a docetaxel-containing regimen (patients who

have received at least 225 mg/m2 (three cycles) of

docetaxel and have an Eastern Cooperative Oncology

Group (ECOG) performance status of 0 or 1).This advice is

contingent upon the continuing availability of the patient

access scheme in NHS Scotland or a list price that is

equivalent or lower.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Solution for infusion

EXCIPIENTS: May contain Ethanol

▶ Jevtana (Sanofi)

Cabazitaxel 40 mg per 1 ml JEVTANA 60mg/1.5ml concentrate and

solvent for solution for infusion vials | 1 vial P £3,696.00

(Hospital only)

Docetaxel 31-Jul-2018

l INDICATIONS AND DOSE

Adjuvant treatment of operable node-positive and

operable node-negative breast cancer (in combination

with doxorubicin and cyclophosphamide)| Initial

chemotherapy of locally advanced or metastatic breast

cancer (with doxorubicin)| Locally advanced or

metastatic breast cancer where cytotoxic chemotherapy

with an anthracycline or an alkylating drug has failed

(monotherapy)| Locally advanced or metastatic breast

cancer where cytotoxic chemotherapy with an

anthracycline has failed (with capecitabine)| Initial

chemotherapy of metastatic breast cancer which

overexpresses human epidermal growth factor-2 (with

trastuzumab)| Locally advanced or metastatic non-small

cell lung cancer where previous chemotherapy has failed

| Initial chemotherapy of unresectable, locally advanced

or metastatic non-small cell lung cancer (with cisplatin)|

Hormone-resistant metastatic prostate cancer (in

combination with prednisone or prednisolone)| Initial

treatment of metastatic gastric adenocarcinoma,

including adenocarcinoma of the gastro-oesophageal

junction (with cisplatin and fluorouracil)| Induction

treatment of locally advanced squamous cell carcinoma

of the head and neck (with cisplatin and fluorouracil)

▶ BY INTRAVENOUS INFUSION

▶ Adult: (consult product literature or local protocols)

l CAUTIONS Avoid in Acute porphyrias p. 1058 . consult

product literature

l INTERACTIONS → Appendix 1: taxanes

l SIDE-EFFECTS

▶ Common or very common Abdominal pain . alopecia . anaemia . appetite decreased . arrhythmia . arthralgia . asthenia . constipation . diarrhoea . dyspnoea . fluid

imbalance . haemorrhage . hypersensitivity . hypertension . hypotension . increased risk of infection . myalgia . nail

disorders . nausea . neutropenia . pain . peripheral

neuropathy . sepsis . skin reactions . stomatitis .taste

altered .thrombocytopenia . vomiting

▶ Uncommon Gastrointestinal disorders . heart failure

▶ Frequency not known Ascites . bone marrow depression . chest tightness . chills . cutaneous lupus erythematosus . disseminated intravascular coagulation . eye disorders . eye inflammation .fever. hearing impairment. hepatitis . hyponatraemia . loss of consciousness . multi organ failure . myocardial infarction . nail discolouration . neurotoxicity . ototoxicity . pericardial effusion . peripheral

lymphoedema . peripheral oedema . pulmonary oedema . radiation injuries .renal impairment.respiratory disorders . sclerodermal-like changes . seizure . sensation abnormal . severe cutaneous adverse reactions (SCARs). vasodilation . venous thromboembolism . vision disorders . weight

increased

SIDE-EFFECTS, FURTHER INFORMATION Pretreatment with

dexamethasone by mouth is recommended for reducing

fluid retention and hypersensitivity reactions.

l CONCEPTION AND CONTRACEPTION Manufacturer advises

effective contraception for men and women during

treatment, and for at least 6 months after stopping

treatment in men.

l PREGNANCY Avoid (toxicity in animal studies). See also

Pregnancy and reproductive function in Cytotoxic drugs

p. 888.

l BREAST FEEDING Discontinue breast-feeding.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

mild to moderate and to avoid in severe impairment.

Dose adjustments Manufacturer advises dose reduction

according to liver function tests in mild to moderate

impairment —consult product literature.

924 Cytotoxic responsive malignancy BNF 78

Immune system and malignant disease

8

Monitoring Monitor liver function in hepatic impairment.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Docetaxel for the treatment of hormone-refractory metastatic

prostate cancer (June 2006) NICE TA101

Docetaxel is an option for hormone-refractory metastatic

prostate cancer only if their Karnofsky score is at least 60%

[Karnofsky score is a measure of the ability to perform

ordinary tasks].

www.nice.org.uk/guidance/ta101

▶ Docetaxel for the adjuvant treatment of early node-positive

breast cancer (September 2006) NICE TA109

Docetaxel, when given concurrently with doxorubicin and

cyclophosphamide (TAC regimen), is recommended as an

option for the adjuvant treatment of women with early

node-positive breast cancer.

www.nice.org.uk/guidance/ta109

▶ Pertuzumab with trastuzumab and docetaxel for treating

HER2-positive breast cancer (March 2018) NICE TA509

Pertuzumab, in combination with trastuzumab and

docetaxel, is recommended, within its marketing

authorisation, for treating HER2-positive metastatic or

locally recurrent unresectable breast cancer, in adults who

have not had previous anti-HER2 therapy or chemotherapy

for their metastatic disease, only if the manufacturer

provides pertuzumab within the agreed commercial access

arrangement.

www.nice.org.uk/guidance/ta509

Scottish Medicines Consortium (SMC) decisions

SMC No. 369/07

The Scottish Medicines Consortium has advised (May 2007)

that docetaxel (Taxotere ®) in combination with cisplatin

and fluorouracil is accepted for restricted use within NHS

Scotland for the induction treatment of patients with

unresectable locally advanced squamous cell carcinoma of

the head and neck.

SMC No. 481/08

The Scottish Medicines Consortium has advised (July

2008) that docetaxel (Taxotere ®) in combination with

cisplatin and fluorouracil is accepted for restricted use

within NHS Scotland for the induction treatment of

patients with resectable locally advanced squamous cell

carcinoma of the head and neck.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Solution for infusion

EXCIPIENTS: May contain Ethanol

▶ Docetaxel (Non-proprietary)

Docetaxel 10 mg per 1 ml Docetaxel 80mg/8ml concentrate for

solution for infusion vials | 1 vial P £534.75 (Hospital only)

Docetaxel 160mg/16ml concentrate for solution for infusion vials | 1 vial P £1,069.50 (Hospital only)

Docetaxel 20mg/2ml concentrate for solution for infusion vials |

1 vial P £162.75 (Hospital only)

Docetaxel 20 mg per 1 ml Docetaxel 80mg/4ml concentrate for

solution for infusion vials | 1 vial P £300.67–£676.44 (Hospital

only) | 1 vial P £479.06–£530.00

Docetaxel 160mg/8ml concentrate for solution for infusion vials | 1 vial P £601.36–£1,148.65 (Hospital only) | 1 vial P £958.11–

£1,000.00

Docetaxel 140mg/7ml concentrate for solution for infusion vials | 1 vial P £900.00

Docetaxel 20mg/1ml concentrate for solution for infusion vials |

1 vial P £91.51–£194.48 (Hospital only) | 1 vial P £145.80–

£160.00

Paclitaxel 17-Jul-2017

l DRUG ACTION Paclitaxel is a member of the taxane group

of drugs.

l INDICATIONS AND DOSE

Treatment of ovarian cancer (advanced or residual

disease following laparotomy) in combination with

cisplatin (conventional paclitaxel only)| Treatment of

metastatic ovarian cancer where platinum-containing

therapy has failed (conventional paclitaxel only)|

Treatment of locally advanced or metastatic breast

cancer (in combination with other cytotoxics or alone if

other cytotoxics have failed or are inappropriate)

(conventional paclitaxel only)| Adjuvant treatment of

node-positive breast cancer following treatment with

anthracycline and cyclophosphamide (conventional

paclitaxel only)| Treatment of non-small cell lung cancer

(in combination with cisplatin) when surgery or

radiotherapy not appropriate (conventional paclitaxel

only)| Treatment of advanced AIDS-related Kaposi’s

sarcoma where liposomal anthracycline therapy has

failed (conventional paclitaxel only)| First-line

treatment of metastatic adenocarcinoma of the

pancreas (in combination with gemcitabine)

(conventional paclitaxel only)| Monotherapy of

metastatic breast cancer when first-line treatment has

failed and standard, anthracycline-containing therapy is

not indicated (albumin-bound paclitaxel only)| In

combination with gemcitabine for the first-line

treatment of metastatic adenocarcinoma of the

pancreas (albumin-bound paclitaxel only)

▶ BY INTRAVENOUS INFUSION

▶ Adult: (consult product literature or local protocols)

l CAUTIONS Avoid in Acute porphyrias p. 1058 . consult

product literature . patients aged over 75 years with

metastatic adenocarcinoma of the pancreas

l INTERACTIONS → Appendix 1: taxanes

l SIDE-EFFECTS

▶ Common or very common Alopecia . anaemia . anxiety . appetite decreased . arrhythmias . arthralgia . asthenia . bone marrow disorders . chest discomfort. chills . constipation . cough . decreased leucocytes . depression . diarrhoea . dizziness . drowsiness . dry eye . dyspnoea . electrolyte imbalance . excessive tearing . extravasation

necrosis . eye inflammation . fever. fluid imbalance . gastrointestinal discomfort. gastrointestinal disorders . haemorrhage . headache . hyperpyrexia . hypertension . increased risk of infection . influenza like illness . insomnia . laryngeal pain . lymphoedema . malaise . movement

disorders . mucositis . muscle complaints . nail

discolouration . nail disorders . nasal complaints . nausea . nerve disorders . neutropenia . oedema . oral disorders . pain .respiratory disorders . sensation abnormal . skin

reactions .taste altered .thrombocytopenia . vasodilation . vertigo . vision disorders . vomiting . weight changes

▶ Uncommon Allergic rhinitis . breast pain . catheter related

infection . dry mouth . dysphagia . ear pain . embolism and

thrombosis . eye discomfort. facial swelling . gait abnormal . hepatomegaly . hoarseness . hyperglycaemia . hypoalbuminaemia . hypoglycaemia . hypotension . limb

discomfort. muscle weakness . neoplasm complications . peripheral coldness . photosensitivity reaction . polydipsia .reflexes abnormal . sepsis . sweat changes . swelling . syncope .tinnitus .tremor. urinary disorders

▶ Rare or very rare Atrioventricular block . cardiac arrest. congestive heart failure . left ventricular dysfunction . radiation injuries . severe cutaneous adverse reactions

(SCARs)

SIDE-EFFECTS, FURTHER INFORMATION Manufacturer

advises routine premedication with a corticosteroid, an

BNF 78 Cytotoxic responsive malignancy 925

Immune system and malignant disease

8

antihistamine and a histamine H2-receptor antagonist is

recommended to prevent severe hypersensitivity

reactions; hypersensitivity reactions may occur rarely

despite premedication.

l CONCEPTION AND CONTRACEPTION Ensure effective

contraception during and for at least 6 months after

treatment in men or women.

l PREGNANCY Avoid (toxicity in animal studies). See also

Pregnancy and reproductive function in Cytotoxic drugs

p. 888.

l BREAST FEEDING Discontinue breast-feeding.

l HEPATIC IMPAIRMENT (Consult product literature)

l MONITORING REQUIREMENTS

▶ Cardiac monitoring should be undertaken, particularly if

patients have underlying cardiac disease or previous

exposure to anthracyclines.

▶ Patients should be monitored for signs and symptoms of

pneumonitis and sepsis.

l PRESCRIBING AND DISPENSING INFORMATION Paclitaxel is

available as both conventional and albumin-bound

formulations. The different formulations vary in their

licensed indications, pharmacokinetics, dosage and

administration, and are not interchangeable.

Prescribers should specify the brand to be dispensed.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Paclitaxel for ovarian cancer (January 2003) NICE TA55

Either paclitaxel in combination with a platinum

compound (cisplatin or carboplatin) or a platinum

compound alone are alternatives for the first-line

treatment of ovarian cancer (usually following surgery).

www.nice.org.uk/guidance/TA55

▶ Paclitaxel for the adjuvant treatment of early node-positive

breast cancer (September 2006) NICE TA108

Paclitaxel, within its licensed indication, is not

recommended for the adjuvant treatment of women with

early node-positive breast cancer.

www.nice.org.uk/guidance/TA108

▶ Bevacizumab in combination with paclitaxel and carboplatin

for the first-line treatment of advanced ovarian cancer (May

2013) NICE TA284

Bevacizumab in combination with paclitaxel and

carboplatin is not recommended for the first-line

treatment of advanced ovarian cancer (including fallopian

tube and primary peritoneal cancer).

www.nice.org.uk/guidance/TA284

▶ Topotecan, pegylated liposomal doxorubicin hydrochloride,

paclitaxel, trabectedin and gemcitabine for treating recurrent

ovarian cancer (April 2016) NICE TA389

Paclitaxel, in combination with platinum or as

monotherapy, is recommended as an option for treating

recurrent ovarian cancer.

www.nice.org.uk/guidance/TA389

▶ Paclitaxel as albumin-bound nanoparticles with gemcitabine

for untreated metastatic pancreatic cancer (September 2017)

NICE TA476

Paclitaxel as albumin-bound nanoparticles (nabpaclitaxel) with gemcitabine is recommended as an option

for untreated metastatic adenocarcinoma of the pancreas

in adults, only if:

. other combination chemotherapies are unsuitable and

they would otherwise have gemcitabine monotherapy,

and

. the manufacturer provides nab-paclitaxel with the

discount agreed in the patient access scheme.

Patients whose treatment with nab-paclitaxel was started

before this guidance was published, should have the

option to continue treatment until they and their NHS

clinician consider it appropriate to stop.

www.nice.org.uk/guidance/TA476

Scottish Medicines Consortium (SMC) decisions

The Scottish Medicines Consortium has advised (April 2010)

that paclitaxel albumin (Abraxane ®) is accepted for

restricted use within NHS Scotland for treatment of

metastatic breast cancer in patients who have failed firstline treatment for metastatic disease and for whom

standard anthracycline containing therapy is not

indicated; use is restricted to patients who would

otherwise receive docetaxel or 3-weekly solvent-based

paclitaxel as second-line treatment for metastatic breast

cancer.

The Scottish Medicines Consortium has advised (February

2015) that paclitaxel albumin (Abraxane ®) is accepted for

use within NHS Scotland in combination with gemcitabine

for the first-line treatment of adult patients with

metastatic adenocarcinoma of the pancreas.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Solution for infusion

EXCIPIENTS: May contain Polyoxyl castor oils

▶ Paclitaxel (Non-proprietary)

Paclitaxel 6 mg per 1 ml Paclitaxel 150mg/25ml concentrate for

solution for infusion vials | 1 vial P £504.90–£561.00 (Hospital

only) | 1 vial P £300.52

Paclitaxel 30mg/5ml concentrate for solution for infusion vials | 1 vial P £112.31–£116.05 (Hospital only) | 1 vial P £66.85

Paclitaxel 100mg/16.7ml concentrate for solution for infusion vials | 1 vial P £336.60–£374.00 (Hospital only) | 1 vial P £200.35–

£342.59

Paclitaxel 300mg/50ml concentrate for solution for infusion vials | 1 vial P £1,009.80–£1,122.00 (Hospital only) | 1 vial P £601.03

Powder for suspension for infusion

ELECTROLYTES: May contain Sodium

▶ Abraxane (Celgene Ltd)

Paclitaxel albumin 100 mg Abraxane 100mg powder for suspension

for infusion vials | 1 vial P £246.00 (Hospital only)

ANTINEOPLASTIC DRUGS › TOPOISOMERASE I

INHIBITORS

Irinotecan hydrochloride 15-Apr-2019

l DRUG ACTION Irinotecan inhibits topoisomerase I, an

enzyme involved in DNA replication.

l INDICATIONS AND DOSE

Metastatic colorectal cancer in combination with

fluorouracil and folinic acid or as monotherapy when

treatment containing fluorouracil has failed | Treatment

of epidermal growth factor receptor-expressing

metastatic colorectal cancer after failure of

chemotherapy that has included irinotecan (in

combination with cetuximab)| First-line treatment of

metastatic carcinoma of the colon or rectum (in

combination with fluorouracil, folinic acid and

bevacizumab)| First-line treatment of metastatic

colorectal carcinoma (in combination with capecitabine

with or without bevacizumab)

▶ BY INTRAVENOUS INFUSION

▶ Adult: (consult product literature or local protocols)

926 Cytotoxic responsive malignancy BNF 78

Immune system and malignant disease

8

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