Education of patients taking capecitabine

EORTC 10041 BIG 3-04 Intergroup Study

MINDACT (Microarray In Node-negative Disease may Avoid ChemoTherapy):

A prospective, randomized study comparing the 70-gene signature with the common clinical-pathological criteria in selecting patients for adjuvant

chemotherapy in node-negative breast cancer

Oral capecitabine = chemotherapy at home

• Treatment with capecitabine is home-based

• The patient takes an active role in treatment administration

• The patient must take an active role in the management of toxicity

• The patient must receive proper education to manage home-based chemotherapy

Treatment interruptions prevent worsening toxicity

• Studies show that

– if capecitabine is interrupted at onset of toxicity, it usually resolves quickly (2-3 days)

– capecitabine can be re-started at same dose

– if capecitabine is not interrupted in time, toxicity worsens and may lead to permanent treatment discontinuation

Blum JL et al. J Clin Oncol 1999; 17: 485-93 Cassidy J et al. Ann Oncol 2002;13:566–75

Patients need to understand importance of early capecitabine interruption

• Patients

– may not easily accept the idea of interrupting

capecitabine

– are often prepared to experience toxicities and do not want to interrupt treatment for fear it may decrease efficacy

• Not accepting short interruptions is counter-productive as it may lead to increased toxicity and treatment discontinuation or low dose intensity

Patients must be reassured that protocol compliant dose modifications

will not compromise efficacy

No. of patients

100

80

60

40

20

0Before After Before After Before After

Hand-foot syndrome Diarrhea Stomatitis

Grade 2

Grade 3

Grade 4

Capecitabine dose modification reduces the recurrence of adverse events

Cassidy J et al. Ann Oncol 2002;13:566–75

Capecitabine dose modification does not compromise efficacy

Decreased risk of disease

progression

Increased risk of disease

progression

No difference in risk of disease

progression

capecitabineHR=0.97p=0.78

5-FU/LV HR=1.12

p=NS

HR = hazard ratio for disease progressionin patients with versus without dose reduction Cassidy J et al. Ann Oncol 2002;13:566–75

Detailed instructions should be given to patients

• If patients experience any of the following– moderate diarrhea (increase of 4 to 6 stools

a day) and/or diarrhea at night– 2-5 vomiting episodes in 24 hours – pain, redness and/or swelling of the mouth– pain, swelling and redness of the hands or

feet

If grade 2 non-hematologic toxicity, patient should stop capecitabine and call you

• They should – STOP taking capecitabine – TELEPHONE their investigator / study nurse

immediately– Begin treatment if available– Drink plenty of water ( 2L/day)

Phone contact permits investigator / study nurse to advise patient on further management

• The investigator / study nurse can advise on– treatment at home – set appointment for further phone follow-up– re-starting capecitabine – need to come to the clinic for further

assessment – possibly hospitalization

Proactive patient contact may further improve patient management

• Sites contacting patients on a regular basis proactively between clinic visits might discover potential adverse events earlier, resulting in– earlier treatment, decreased duration of treatment

and/or less aggressive treatment of adverse event– reduction in number of adverse events reaching

grade 3 / 4 severity

– decreased possibility that capecitabine dose will have to be held or reduced in order to manage the event

– increased patient comfort and confidence in taking a home-based chemotherapy

Grade 2, 3, or 4 non-hematologic toxicity

• Diarrhea

• Nausea / vomiting *

• Stomatitis / mucositis

• Hand-foot syndrome

Interrupt capecitabine for grade 2 non-hematologic toxicities

INTERRUPT

CAPECITABINE

IMMEDIATELY

* Occuring under adequate antiemetic treatmentNote per MINDACT protocol: sites should follow local guidelines – antiemetics and/or corticoids

GI toxicity requires prompt management

• The most common problem is GI toxicity: diarrhea, nausea, vomiting

• In case of diarrhea grade ≥ 2 patients should be instructed to STOP taking capecitabine and START taking loperamide

• If diarrhea is not properly managed it may worsen, leading to life-threatening dehydration and even death

Supportive management of diarrhea in MINDACT: loperamide and fluids

• Loperamide (patient should have at home)

– 4 mg first onset, then 2 mg every 2 hours until 12 hours after last loose stool (total treatment duration should not exceed 48 hrs)

– Do not re-start capecitabine until diarrhea has resolved to < grade 1 with the last loperamide dose given at least 24 hours beforehand

– prophylaxis not recommended

– laxatives should not be used

Note: under Capecitabine monotherapy 2mg Loperamide every 6 hrs is usually enough to successfully treat diarrhea

Supportive management of diarrhea cont.: loperamide and fluids

• Tell patient to drink at least 2 L water per day

• Hospitalization with fluid and electrolyte support when clinically indicated or diarrhea persists after 48 hrs of recommended Loperamide treatment

Management of other non-hematological adverse events grade 2

In case of grade ≥ 2 Patients should STOP taking capecitabine and start

Nausea/vomiting * Anti-emetics, suitable food & drink

Mucositis/Stomatitis Mouth washes,suitable food & drink

Hand-foot-syndrome Skin emollients, avoid putting pressure on palms and soles

* Note per MINDACT protocol: sites should follow local guidelines – antiemetics and/or corticoids

Dose-reduction tables

If dosereductions are necessary please use the following dose

reduction tables

Pill combinations to be taken based on a 25% dosereduction for capecitabine (620 mg/m2 bid)

Body Surface Area (m2)

Total dose per administration

(mg)

Morning pills Evening pills

150 mg 500 mg 150 mg 500 mg

< 1.48 800 2 1 2 1

1.49 – 1.69 1000 0 2 0 2

1.70 – 1.90 1150 1 2 1 2

1.91 – 2.30 1300 2 2 2 2

> 2.31 1500 0 3 0 3

75% dose level

Pill combinations to be taken based on a 50% dosereduction for capecitabine (412.5 mg/m2 bid)

Body Surface Area (m2)

Total dose per administration

(mg)

Morning pills Evening pills

150 mg 500 mg 150 mg 500 mg

< 1.48 500 0 1 0 1

1.49 – 1.69 650 1 1 1 1

1.70 – 2.30 800 2 1 2 1

> 2.31 1000 0 2 0 2

50% dose level

Patient education must be clear and face-to-face

• The educator should take enough timeto inform patients

• A longer initial information session is a good investment

• Avoid fragmentation of information (several persons giving pieces of information without coordinating their efforts)

• Repeat information during treatment

• Establish clear communication lines

Use the available tools

• Patients should have written information leaflets at home as a reminder of the information received at the site

• Educators should use the provided check lists for patient education

Patient education is an integral part of capecitabine treatment