Presentation on theme: "Education of patients taking capecitabine"— Presentation transcript:
1Education of patients taking capecitabine These slides focus on the importance of patient education for managing toxicity related to capecitabine.Extra details particularly relevant to the MINDACT protocol have been added when applicable.EORTC BIG 3-04 Intergroup StudyMINDACT (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
2Oral capecitabine = chemotherapy at home Treatment with capecitabine is home-basedThe patient takes an active role in treatment administrationThe patient must take an active role in the management of toxicityThe patient must receive proper education to manage home-based chemotherapyUnlike intravenous chemotherapy, capecitabine is administered as tablets at home and therefore the patient has an active role in treatment administration.To a higher degree compared with intravenous chemotherapy, the patient must take an active role in the management of toxicity.Considering the active role of the patient for both treatment administration and management of toxicity, it is of crucial importance that the patient receives proper education to manage home-based chemotherapy.
3Treatment interruptions prevent worsening toxicity Studies show thatif capecitabine is interrupted at onset of toxicity, it usually resolves quickly (2-3 days)capecitabine can be re-started at same doseif capecitabine is not interrupted in time, toxicity worsens and may lead to permanent treatment discontinuationInterruption of capecitabine at onset of moderate (grade 2) toxicity is the most common way to manage toxicity.Brief drug interruptions and/or dose adjustments lead to the reinstitution of treatment in most patients.If capecitabine is not interrupted at onset of moderate toxicity, the toxicity may worsen and may lead to permanent treatment discontinuation.Blum JL et al. J Clin Oncol 1999; 17:Cassidy J et al. Ann Oncol 2002;13:566–75
4Patients need to understand importance of early capecitabine interruption may not easily accept the idea of interrupting capecitabineare often prepared to experience toxicities and do not want to interrupt treatment for fear it may decrease efficacyNot accepting short interruptions is counter-productive as it may lead to increased toxicity and treatment discontinuation or low dose intensityPatients with cancer are usually prepared to accept treatment toxicity and fear that interruption of treatment may decrease efficacy. Therefore they may not easily accept to interrupt capecitabine at onset of moderate toxicity.It is one of the main tasks of the educator to make the patient understand that capecitabine must be interrupted at onset of moderate toxicity. Not respecting this rule may lead to increased toxicity and either treatment discontinuation or low dose intensity because dose reductions will be needed in case of severe and/or life threatening toxicity.
5Patients must be reassured that protocol compliant dose modifications will not compromise efficacy It is very important to inform and reassure the patients that the dose modifications according to the protocol (interruptions and dose reductions due to toxicity) will not compromise efficacy.
6Capecitabine dose modification reduces the recurrence of adverse events No. of patients10080604020Grade 2Grade 3Grade 4Analyses performed in previous trials show that dose modifications due to toxicity reduce the recurrence of toxicity. Presented here is the analysis of the impact of dose modification on recurrence of hand foot syndrome, diarrhea and stomatitis. This analysis was performed in patients treated with capecitabine monotherapy in two clinical trials in metastatic colorectal cancer and it is a part of the integrated safety analysis of these two trials published in Annals of Oncology 2002 (Cassidy J et al.)Before After Before After Before AfterHand-foot syndrome Diarrhea StomatitisCassidy J et al. Ann Oncol 2002;13:566–75
7Capecitabine dose modification does not compromise efficacy HR=0.97p=0.785-FU/LVHR=1.12p=NSDecreased riskof diseaseprogressionIncreased riskof diseaseprogressionNo difference inrisk of diseaseprogressionAnalyses performed in previous trials show that dose modifications of capecitabine due to toxicity do not compromise efficacy. Presented here is the analysis of the impact of dose modification on treatment efficacy in terms of time to disease progression. This analysis was also performed in patients treated with capecitabine monotherapy in two clinical trials in metastatic colorectal cancer being a part of the integrated safety analysis of these two trials published in Annals of Oncology 2002 (Cassidy J et al.)HR = hazard ratio for disease progression in patients with versus without dose reductionCassidy J et al. Ann Oncol 2002;13:566–75
8Detailed instructions should be given to patients If patients experience any of the followingmoderate diarrhea (increase of 4 to 6 stools a day) and/or diarrhea at night2-5 vomiting episodes in 24 hourspain, redness and/or swelling of the mouthpain, swelling and redness of the hands or feetThe intensity of diarrhea, nausea/vomiting, stomatitis and is described in CTCAE v.3 and patients must learn what exactly is moderate (grade 2) intensity for these key toxicities.For diarrhea, moderate intensity means increase of 4-6 stools/day compared to the stool habits before treatment start and/or diarrhea at night. This is a relative scale.For nausea/vomiting, moderate intensity means 2-5 vomiting episodes in 24 hours.The patient must also recognize- moderate stomatitis: pain, redness and/or swelling of the mouth- moderate hand foot syndrome: pain, swelling and redness of the hands and feet.
9If grade 2 non-hematologic toxicity, patient should stop capecitabine and call you They shouldSTOP taking capecitabineTELEPHONE their investigator / study nurse immediatelyBegin treatment if availableDrink plenty of water ( 2L/day)The patients must get clear instruction what to do at onset of moderate toxicity. To stop capecitabine is the right action but not the only one. The patients must also get in touch with their investigator / study nurse and the quickest way is to use the telephone.For some but not all toxicities treatment is available. If treatment is available the patients should have the medication at home and start using it at onset of moderate toxicity.As a general recommendation: remind the patient to drink plenty of water.
10The investigator / study nurse can advise on treatment at home Phone contact permits investigator / study nurse to advise patient on further managementThe investigator / study nurse can advise ontreatment at homeset appointment for further phone follow-upre-starting capecitabineneed to come to the clinic for further assessmentpossibly hospitalizationThe contact with the investigator / study nurse is very important as, depending of the nature and intensity of the toxicity, treatment may be given at home or the patients must come to the clinic for further assessment which may lead to hospitalization.It is important to set appointments for further phone follow-up. Thus further instructions can be communicated depending on the clinical development. If toxicity resolves patients may be advised to re-start capecitabine.
11Proactive 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 inearlier treatment, decreased duration of treatment and/or less aggressive treatment of adverse eventreduction in number of adverse events reaching grade 3 / 4 severitydecreased possibility that capecitabine dose will have to be held or reduced in order to manage the eventincreased patient comfort and confidence in taking a home-based chemotherapy
12Interrupt capecitabine for grade 2 non-hematologic toxicities Grade 2, 3, or 4 non-hematologic toxicityDiarrheaNausea / vomiting *Stomatitis / mucositisHand-foot syndromeINTERRUPTCAPECITABINEIMMEDIATELYThe key toxicities are non-hematologic: diarrhea, nausea/vomiting, stomatitis and hand foot syndrome. The patient must learn to recognize the onset of moderate intensity of these toxicities and stop capecitabine if toxicity occurs during treatment.The MINDACT protocol does not necessarily require interruption of capecitabine for nausea / vomiting. Sites should follow local guidelines.* Occuring under adequate antiemetic treatment Note per MINDACT protocol: sites should follow local guidelines – antiemetics and/or corticoids
13GI toxicity requires prompt management The most common problem is GI toxicity: diarrhea, nausea, vomitingIn case of diarrhea grade ≥ 2 patients should be instructed to STOP taking capecitabine and START taking loperamideIf diarrhea is not properly managed it may worsen, leading to life-threatening dehydration and even deathThe most common toxicity with capecitabine is gastro-intestinal, especially diarrhea. In case of moderate or more intensive (grade 2 or more) diarrhea, patients must stop capecitabine and start taking loperamide.Diarrhea is potentially dangerous. If not properly managed it may worsen leading to life-threatening dehydration and even death.
14Supportive 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 beforehandprophylaxis not recommendedlaxatives should not be usedNote: under Capecitabine monotherapy 2mg Loperamide every 6 hrs is usually enough to successfully treat diarrheaThe patients must have loperamide (Imodium) at home and get clear instructions how to use it: 4 mg (2 tablets) at onset then 2 mg (1 tablet) every 2 hrs (combination therapy) or every 6th hour (monotherapy) until 12 hours after last loose stool. Prophylactic treatment with loperamide in absence of diarrhea is not recommended as it can lead to constipation and in worst case to intestinal obstruction.The high dose loperamide regimen recommende in the Mindact protocol should not be used longer than 48 hours.
15Supportive management of diarrhea cont.: loperamide and fluids Tell patient to drink at least 2 L water per dayHospitalization with fluid and electrolyte support when clinically indicated or diarrhea persists after 48 hrs of recommended Loperamide treatmentRemind the patients to drink at least 2 L water per day.Patients should not only stop capecitabine and start loperamide but make contact with the investigator / study nurse. If clinically indicated, the patients may need hospitalization for fluid and electrolyte support.The MINDACT protocol requires that patients be hospitalized for parenteral support if diarrhea persists for more than 48 hours.
16Management of other non-hematological adverse events grade 2 In case of grade ≥ 2Patients should STOP taking capecitabine and startNausea/vomiting *Anti-emetics, suitable food & drinkMucositis/StomatitisMouth washes, suitable food & drinkHand-foot-syndromeSkin emollients, avoid putting pressure on palms and solesTreatment is available not only for diarrhea but also for nausea/vomiting, stomatitis and hand foot syndrome.In case of nausea of moderate or worse intensity (grade 2 or more), patients should start treatment with antiemetics at home. Give also advice about suitable food and drink.The MINDACT protocol does not necessarily require interruption of capecitabine for nausea / vomiting. Sites should follow local guidelines.In case of stomatitis of moderate or worse intensity (grade 2 or more), patients should start treatment with mouth washes. Give also advice about suitable food and drink.For moderate or worse intensity (grade 2 or more) hand foot syndrome, patients should use skin emollients (e.g., E-45 or Neutrogena skin cream). Give also advice to avoid very hot water, abrasives and putting pressure on palms and soles.* Note per MINDACT protocol: sites should follow local guidelines – antiemetics and/or corticoids
17Dose-reduction tables If dosereductions are necessary please use the following dose reduction tables
18Total dose per administration (mg) Pill combinations to be taken based on a 25% dosereduction for capecitabine (620 mg/m2 bid)75% dose levelBody Surface Area (m2)Total dose per administration (mg)Morning pillsEvening pills150 mg500 mg< 1.48800211.49 – 1.6910001.70 – 1.9011501.91 – 2.301300> 2.3115003Use this dosing table in patients who require a 25% decrease in their capecitabine dose.
19Total dose per administration (mg) Pill combinations to be taken based on a 50% dosereduction for capecitabine (412.5 mg/m2 bid)50% dose levelBody Surface Area (m2)Total dose per administration (mg)Morning pillsEvening pills150 mg500 mg< 1.4850011.49 – 1.696501.70 – 2.308002> 2.311000Use this dosing table in patients who require a 50% decrease in their capecitabine dose.
20Patient education must be clear and face-to-face The educator should take enough time to inform patientsA longer initial information session is a good investmentAvoid fragmentation of information (several persons giving pieces of information without coordinating their efforts)Repeat information during treatmentEstablish clear communication linesPatient education is very important for safe administration of capecitabine. The educator should allocate enough time for patient information / education. The amount of time may vary between patients. A longer initial information session is necessary and is a good investment for treatment safety.Avoid fragmentation of information. If several persons give information, coordinate their efforts.Information must be repeated during treatment.The patient should know whom to ask: establish clear communication lines.
21Use the available tools Patients should have written information leaflets at home as a reminder of the information received at the siteEducators should use the provided check lists for patient educationUse the available education material: patients should have written information leaflets at home. This is a reminder of the information received at the study site.Use the recently provided checklist for patient education.For the educators, the study protocol and CTCAE v.3 should be easily accessible.
22Patient education is an integral part of capecitabine treatment