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Nausea and vomiting are frequently occurring problems in the palliative phase of patients with cancer. Between 20-50% of them regularly suffer from nausea, retching or vomiting. Often the cause of nausea and vomiting is multifactorial and symptomatic treatment is necessary.
Potential drugs for symptomatic anti-nausea therapy are metoclopramide, serotonin antagonists, the combination of both and dexamethasone as rescue medication in case of failure. There is no data that depicts which strategy is the best. This study will be conducted to unravel which treatment algorithm is most successful.
Nausea and vomiting are frequently occurring problems in the palliative phase of patients with cancer. Between 20-50% of them regularly suffer from nausea, retching or vomiting. Often the cause of nausea and vomiting is multifactorial and symptomatic treatment is necessary.
Potential drugs for symptomatic anti-nausea therapy are metoclopramide, serotonin antagonists, the combination of both and dexamethasone as rescue medication in case of failure. There is no data that depicts which strategy is the best. This study will be conducted to unravel which treatment algorithm is most successful: 1 to start with metoclopramide, to add a serotonin antagonist (granisetron transdermal patch and 2 milligram granisetron oral loading dose if the patient can swallow) in case of failure and to add dexamethasone as rescue medication versus 2 an algorithm to start with a serotonin antagonist (granisetron transdermal patch and 2 milligram granisetron oral loading dose if the patient can swallow), to add metoclopramide in case of failure and to add dexamethasone as rescue medication. Granisetron plaster is a new formulation of a well known serotonin antagonist and might be useful especially within the patient group in the palliative phase.
The questions are:
Is it feasible to compare treatment algorithms for symptomatic treatment of nausea and vomiting in palliative cancer patients? And is a stepwise symptomatic treatment algorithm to manage nausea and vomiting using metoclopramide or granisetron transdermal patch as a start medication effective in palliative patients in at least one of both treatment arms? Patients will be asked to complete the QLQC30 and ESAS on different moments during the study. Besides, they will be asked to complete a diary for nausea severity (NRS scale 0-10) and for the frequency of vomiting and retching twice daily.
Success of a treatment algorithm is defined as nausea is < 3 on NRS or a decrease of >2 on NRS for nausea combined with an absence of vomiting or retching in the last 3 days. Incomplete success is defined as nausea of 3 on NRS during one occasion of the last 3 days before the end of study but less than 4, no more than one retching a day during that period and absence of vomiting. Complete failure is defined as nausea of 4 or more on an NRS during the last 3 days or more than one retching daily or any vomiting or in case the patient has stopped all medication due to side effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| algorithm 1 first metoclopramide | Active Comparator | metoclopramide 10 mg tablets 3x daily orally and in those patients that cannot swallow tablets the medication will be substituted by suppositories 10 mg 3x daily rectally. In case of failure, granisetron patch 3.1mg/24 hours will be added to the treatment and a loading dose of 2 mg granisetron oral if the patient can swallow. In case of toxicity metoclopramide will be stopped. In case of failure of the combination (second step) or toxicity, an oral dose of dexamethasone 8 mg will be added daily. |
|
| algorithm 2 first granisetron | Active Comparator | granisetron patch 3.1 mg/24 hours will be offered to the patient, and a loading dose of 2 mg granisetron oral if the patient can swallow In case of failure, metoclopramide 10 mg tablets 3x daily orally will be added and in those patients that cannot swallow tablets the oral medication will be substituted with rectal suppositories 10 mg. The granisetron patch will only be withdrawn from patients that suffer from clinically relevant toxicity. Metoclopramide will then be administered. In the case of secondary failure or toxicity, dexamethasone 8 mg orally daily will be added. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| metoclopramide | Drug | metoclopramide 10 mg tablets 3x daily orally or suppositories 10 mg 3x daily rectally, use until toxicity |
|
| Measure | Description | Time Frame |
|---|---|---|
| NRS nausea | response defined as NRS <3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days | 15 days |
| Measure | Description | Time Frame |
|---|---|---|
| days from T0 to control | The time from T0 until the moment that nausea and vomiting/retching is in control | two weeks |
| Measure | Description | Time Frame |
|---|---|---|
| feasibility | number of included patients a 6 months period | 6 months |
| comparison of starting metoclopramide to starting with granisetron | response defined as NRS <3 or decrease of more than 2 on NRS and absence of vomiting or retching in the last 3 days |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Christa v Schaik | Contact | 024-3610353 | christa.vanschaik@radboudumc.nl | |
| C.A.H.H.V.M. Verhagen, M.D. Ph.D. | Contact | 024-3610353 | Stans.verhagen@radboudumc.nl |
| Name | Affiliation | Role |
|---|---|---|
| C.A.H.H.V.M. Verhagen, M.D. Ph.D. | Radboud University Medical Center | Principal Investigator |
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| ID | Term |
|---|---|
| D009325 | Nausea |
| D014839 | Vomiting |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008787 | Metoclopramide |
| D017829 | Granisetron |
| D003907 | Dexamethasone |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D062366 | para-Aminobenzoates |
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| granisetron | Drug | granisetron patch 3.1mg/24 hours, use until toxicity |
|
|
| Dexamethasone | Drug | dexamethasone 8 mg, last step in both algorithms |
|
| Granisetron 2Mg Tablet | Drug | granisetron 2 mg loading dose |
|
| 6 months |
| quality of life | QLQC30 scale | 15 days |
| adverse events | diary adverse events | 14/15 days |
| D062365 |
| Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D002723 | Chlorobenzoates |
| D062425 | Hydroxybenzoate Ethers |
| D062385 | Hydroxybenzoates |
| D006880 | Hydroxy Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010647 | Phenyl Ethers |
| D010636 | Phenols |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D007191 | Indazoles |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |