Management of Side Effects of Cancer Therapy and Radiation Therapy
Clinical Snapshot
Radiation therapy and pharmacologic cancer therapy — conventional cytotoxic chemotherapy and the growing range of targeted small-molecule and biologic agents — cause toxicities that are, in large part, predictable extensions of how these treatments work. Cytotoxic chemotherapy exploits the high proliferation rate of cancer cells, but the same mechanism damages other rapidly-dividing normal tissue: the oral and gastrointestinal mucosa, the skin and its appendages, and the bone marrow. Radiation causes locally-confined injury along its entry-to-exit path through tissue, with early toxicities appearing within days to months and delayed toxicities appearing months to years later. Targeted agents cause a different, drug-specific toxicity pattern rather than the classic cytotoxic pattern, but the management principle is the same: most of these toxicities are foreseeable, and a pharmacist who anticipates them, counsels proactively, and intervenes early can prevent an unplanned dose reduction, treatment delay, or discontinuation of otherwise effective anticancer therapy.[1] This chapter covers oral mucositis, chemotherapy-induced diarrhea, hand-foot syndrome/hand-foot skin reaction, radiation dermatitis, chemotherapy-induced peripheral neuropathy, the emergency recognition of febrile neutropenia, and extravasation of vesicant chemotherapy — plus the patient-education and self-monitoring counselling role woven through all of them. Chemotherapy-induced nausea and vomiting is covered separately in its own chapter and is not duplicated here.
Recognize the Condition
Severity for each toxicity below is generally described using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade 1-5 scale: Grade 1 is mild and usually needs no intervention; Grade 2 is moderate and may limit instrumental activities of daily living; Grade 3 is severe, limits self-care, and often needs hospitalization or urgent intervention; Grade 4 is life-threatening; Grade 5 is death. Specific grade thresholds that change management are called out within each toxicity below rather than reproduced here as one generic table.[2]
The toxicity syndromes covered in this chapter
Oral mucositis
Erythema progressing to ulceration of the oral mucosa, painful enough at higher grades to interfere with eating, drinking, and swallowing oral medications. Onset is typically days to weeks after starting a mucotoxic regimen, or during head and neck radiation.
Chemotherapy-induced diarrhea
Increased stool frequency and looseness above the patient's baseline. Irinotecan causes an early-onset, cholinergically-mediated diarrhea during or immediately after infusion, distinct from the more common delayed-onset diarrhea seen with most cytotoxic regimens days later.
Hand-foot syndrome and hand-foot skin reaction
Hand-foot syndrome (palmar-plantar erythrodysesthesia), from capecitabine, fluorouracil, or liposomal doxorubicin, is symmetric erythema, edema, and dysesthesia of the palms and soles, progressing to pain, blistering, and desquamation. Hand-foot skin reaction, a related but distinct entity from BRAF inhibitors and multikinase VEGF inhibitors, tends toward localized hyperkeratosis and callus formation at pressure points rather than diffuse erythema.
Radiation dermatitis
Confined to the radiation field, and to the exit point for deeper fields. Ranges from erythema and dry desquamation through moist desquamation to, rarely, ulceration; onset is during treatment through several weeks after.
Chemotherapy-induced peripheral neuropathy (CIPN)
Symmetric, distal, stocking-glove sensory changes — numbness, tingling, sometimes pain — with motor and autonomic involvement less common. Oxaliplatin additionally causes an acute, cold-triggered laryngopharyngeal dysesthesia distinct from its own separate cumulative-dose sensory neuropathy.
Febrile neutropenia
Fever in a patient with a significantly reduced neutrophil count is a medical emergency, not a symptom to monitor at home — see Red Flags & Refer.
Extravasation
Leakage of an infused chemotherapy drug from the vein into surrounding tissue, recognized by pain, burning, swelling, or loss of blood return at the infusion site during or shortly after administration.
Risk Factors
- Oral mucositis: most traditional cytotoxic chemotherapy regimens carry some risk (severity varies by agent and individual); higher-risk classes include mTOR inhibitors, EGFR inhibitors, CDK4/6 inhibitors, and BCL-2 inhibitors; head and neck or upper gastrointestinal radiation; poor baseline oral hygiene or pre-existing dental disease.
- Chemotherapy-induced diarrhea: essentially all traditional cytotoxic agents carry some dose-related risk; irinotecan-based and fluoropyrimidine-based regimens are particularly implicated; pelvic or abdominal radiation.
- Hand-foot syndrome/HFSR: capecitabine, fluorouracil, and liposomal doxorubicin for classic hand-foot syndrome; BRAF inhibitors and multikinase VEGF inhibitors for hand-foot skin reaction; friction or heat exposure to palms/soles during treatment.
- Radiation dermatitis: higher total radiation dose and fraction size; treatment field location, especially skin folds (breast, axilla, groin, neck); concurrent chemotherapy or targeted therapy; prior radiation to the same field; smoking; larger breast size in breast radiation.
- Chemotherapy-induced peripheral neuropathy: cumulative dose of a neurotoxic agent (platinums, taxanes, vinca alkaloids, proteasome inhibitors); pre-existing peripheral neuropathy of any cause, including diabetic neuropathy; combination regimens using more than one neurotoxic agent.
- Febrile neutropenia: regimen- and individual-specific neutropenia risk; dose-dense or heavily myelosuppressive regimens; a prior episode of febrile neutropenia on the same regimen; poor baseline marrow reserve.
- Extravasation: peripheral rather than central venous access for a vesicant drug; fragile, small, or previously-used veins; a patient unable to report pain/burning during infusion; a prolonged infusion through a peripheral line.
Red Flags & Refer
Any of the following in a patient on active cancer therapy needs immediate escalation, not a wait-and-see approach:
- Fever in a neutropenic patient — a single temperature of 38.3°C or higher, or 38.0°C or higher sustained for at least one hour, in a patient with an absolute neutrophil count under 0.5 x10^9/L (or under 1.0 x10^9/L with an expected drop below that within 48 hours) is febrile neutropenia: a true medical emergency requiring immediate assessment and empiric broad-spectrum antibiotics, never "wait and see if it settles." Direct the patient to emergency care or their cancer centre's urgent-access line immediately — see Infections in the Cancer Patient for the full workup and antibiotic selection.[3]
- Severe or refractory oral mucositis preventing adequate oral intake of fluids, food, or medications.
- Signs of extravasation injury — increasing pain, burning, swelling, blistering, or skin breakdown at or around an infusion site, during or after chemotherapy administration.
- Severe, uncontrolled diarrhea with signs of dehydration (dizziness, reduced urine output, orthostatic symptoms) or diarrhea accompanied by fever, blood in the stool, or severe abdominal pain.
- Diarrhea, mucositis, or a skin reaction with widespread blistering or mucosal involvement suggestive of a severe cutaneous drug reaction rather than a routine toxicity.
- New or rapidly progressive weakness, gait instability, or falls in a patient with peripheral neuropathy — this needs prompt reassessment of the causative regimen, not routine follow-up.
Assessment & Diagnosis
Distinguishing hand-foot syndrome from hand-foot skin reaction
| Feature | Hand-foot syndrome (HFS) | Hand-foot skin reaction (HFSR) |
|---|---|---|
| Typical causative drugs | Capecitabine, fluorouracil, liposomal doxorubicin | BRAF inhibitors, multikinase VEGF inhibitors |
| Distribution | Diffuse across palms/soles | Localized to pressure-bearing points (heels, metatarsal heads, sides of fingers) |
| Appearance | Symmetric erythema, edema, dysesthesia; may blister/desquamate | Hyperkeratosis and callus-like thickening, often with a surrounding erythematous rim |
| Typical onset | Cumulative over weeks to months | Can appear within the first 2-4 weeks |
Distinguishing chemotherapy-induced diarrhea from an infectious cause
Do not automatically attribute new diarrhea in a patient on active cancer therapy to the chemotherapy itself. Obtain stool culture and Clostridioides difficile toxin/PCR testing when any of the following are present: fever, recent antibiotic use or hospitalization, blood in the stool, grade 3 or higher diarrhea, or diarrhea in a neutropenic patient — testing is not routinely needed for mild, uncomplicated diarrhea that is temporally linked to a known diarrheagenic regimen and has none of these features.[4]
History and examination
- Confirm the timing of new symptoms relative to the most recent treatment cycle or radiation fraction, and identify the specific causative agent(s) in the regimen.
- Ask specifically about oral intake (mucositis), stool frequency/consistency and hydration status (diarrhea), palm/sole symptoms and functional impact on grip/walking (HFS/HFSR), the radiation field and any skin-fold involvement (radiation dermatitis), and sensory/motor symptoms plus fall risk (CIPN).
- Examine the oral mucosa directly for erythema, ulceration, and extent; examine palms/soles using the HFS-vs-HFSR pattern above; examine the radiated skin field specifically, not just visible exposed skin; perform a focused sensory examination (light touch, vibration), check deep tendon reflexes, and observe gait for CIPN.
- Review the full medication list for other agents that could compound a given toxicity, e.g. another neurotoxic or nephrotoxic drug alongside a neurotoxic chemotherapy agent.
When testing is not indicated
- Routine imaging is not needed for uncomplicated HFS/HFSR or radiation dermatitis — both are clinical diagnoses based on exposure history and exam findings.
- Nerve conduction studies are not routinely needed for typical CIPN — reserve for atypical presentations or genuine diagnostic uncertainty.
- Stool testing is not needed for mild, uncomplicated diarrhea without the red-flag features above.
Treatment Targets
- Prevent each toxicity where a genuine preventive measure exists, by identifying risk factors before treatment starts.
- Detect toxicity early and treat promptly to reduce severity and prevent downstream complications (dehydration, secondary infection, tissue necrosis).
- Control symptoms adequately to preserve the patient's oral intake, mobility, and quality of life.
- Avoid an unplanned dose reduction, treatment delay, or discontinuation of otherwise effective anticancer therapy caused by a toxicity that could have been prevented or managed proactively.
- Recognize and immediately escalate the toxicities that are true emergencies — febrile neutropenia, severe extravasation injury, severe mucositis preventing intake, and severe diarrhea with dehydration.
Choose Initial Treatment
Oral mucositis — prevention
All patients starting a mucotoxic regimen begin a structured oral-care routine before treatment starts: soft-bristled toothbrush, regular brushing, plain saline or sodium bicarbonate rinses several times daily, and avoidance of alcohol-containing mouthwash; continue throughout treatment.[1]
Bolus fluorouracil or high-dose melphalan regimens specifically add oral cryotherapy — ice chips or ice water held/swished in the mouth starting 5 minutes before the dose and continued for 30 minutes total — which reduces the incidence and severity of mucositis.[1]
Do not use oral cryotherapy or cold foods with an oxaliplatin-containing regimen (e.g. FOLFOX) — oxaliplatin causes a cold-triggered pharyngolaryngeal dysesthesia that cryotherapy can precipitate.
Everolimus and other mTOR inhibitors — an alcohol-free dexamethasone 0.1 mg/mL oral rinse, swished for 2 minutes and spat out four times daily starting on day 1 of cycle 1 and continued through the first several cycles, reduces the incidence and severity of stomatitis.[5]
Do not use chlorhexidine mouth rinse for prevention in patients receiving head and neck radiotherapy — despite historical use, it has specifically not been shown to prevent oral mucositis in this setting.[1]
Oral mucositis — established management
Mild-moderate (grade 1-2), oral intake preserved continue bland saline/bicarbonate rinses and basic oral hygiene, and add benzydamine oral rinse for its topical anti-inflammatory/analgesic effect.
Do not use sucralfate (topical or systemic) for mucositis pain — despite historical use, it has specifically not been shown to prevent or treat mucositis-associated pain.[1]
Severe (grade 3-4) pain, or intake compromised escalate to systemic analgesia including opioids, and involve the oncology team regarding nutrition/hydration support.
Other proposed agents — a 0.5% doxepin oral rinse, viscous barrier gels, and combination ("magic mouthwash") rinses are commonly used in practice, but the trial evidence for each is limited, inconsistent, and the exact combination-rinse formula is institution-specific rather than standardized; use them as adjuncts rather than a substitute for the measures above.[1]
Chemotherapy-induced diarrhea
Uncomplicated diarrhea (grade 1-2, no complicating features) standard-dose loperamide 4 mg orally, then 2 mg after each unformed stool to a maximum of 16 mg over 24 hours, plus oral rehydration.[4]
Irinotecan-based regimens, or any chemotherapy diarrhea not responding to standard-dose loperamide within 24 hours switch to the high-dose loperamide regimen: 4 mg initially, then 2 mg every 2 hours during the day and 4 mg every 4 hours overnight, continued until 12 hours diarrhea-free, for a maximum of 48 hours total. This is a distinct, higher-intensity regimen specific to this indication — it is not standard over-the-counter Imodium dosing.
Do not continue the high-dose loperamide regimen beyond 48 hours without response — continuing longer risks harm without added benefit and delays the escalation that is actually needed.
2nd line, when loperamide is not tolerated or not effective diphenoxylate/atropine 1 tablet (2.5 mg diphenoxylate) orally 3-4 times daily as needed.
Diarrhea persisting despite 48 hours of high-dose loperamide, or complicated diarrhea (grade 3-4, or grade 1-2 with fever, dehydration, bleeding, or severe cramping) hold the causative chemotherapy, obtain stool studies, and start octreotide 100-150 mcg subcutaneously three times daily, escalating up to 500 mcg three times daily if needed, with IV fluids and antibiotics if febrile or neutropenic.[4]
Diarrhea with blood in the stool, abdominal pain, and urgency in a patient on a checkpoint inhibitor, a bispecific T-cell engager, or CAR-T therapy is more likely immune-mediated colitis than classic cytotoxic diarrhea, and needs a different management approach (corticosteroids, possible treatment interruption) rather than the loperamide-based approach above.
Hand-foot syndrome and hand-foot skin reaction
Prevention, from the start of capecitabine or another causative agent apply a plain moisturizer/emollient to palms and soles at least 3 times daily, and avoid prolonged heat or friction exposure to hands and feet.[6]
Topical diclofenac diethylamine 1.16% gel applied to the palms and dorsal/plantar surfaces twice daily from the start of capecitabine reduces the incidence of clinically significant (grade 2-3) hand-foot syndrome and the resulting need for capecitabine dose reduction.[7]
Pyridoxine (vitamin B6) 150-200 mg/day is sometimes prescribed for prevention, but its protective effect is not supported by good-quality evidence — offer it as a low-risk adjunct at most, not as a primary preventive measure.
Established HFS/HFSR continue moisturizer and topical diclofenac gel, add symptomatic analgesia as needed — dose interruption/reduction of the causative agent is what actually resolves it fastest once established.
Grade 2 (pain limiting instrumental activities of daily living) hold the causative drug until resolved to grade 1 or lower, then resume at a reduced dose.
Grade 3 (pain limiting self-care) hold until resolved to grade 1 or lower, resume at a further-reduced dose, or discuss discontinuation with the oncology team if it recurs despite dose reduction.
Radiation dermatitis
All patients, from day 1 of radiation gentle skin care in the field: wash with mild soap or water alone using hands rather than a washcloth, avoid frequent hot showers, wear loose-fitting clothing, moisturize with a plain unscented lanolin-free hydrophilic moisturizer, and protect the field from sun exposure.
Prevention, per the current MASCC Delphi-consensus guideline mometasone or betamethasone applied to the treatment field on radiation treatment days reduces the severity of dermatitis; a silicone-based barrier film (e.g. Mepitel film) additionally reduces incidence specifically in breast radiation.[8]
Not recommended despite historical/traditional use: aloe vera-based products, honey-based products, and vitamin C or vitamin D preparations — current consensus evidence found against all of them for both prevention and management of radiation dermatitis.[8]
Established erythema/pruritus a low-potency topical corticosteroid (hydrocortisone) for symptom relief, used for up to 8 weeks.
Moist desquamation switch from dry-skin-care measures to moist-wound-healing dressings (hydrogel or hydrocolloid products), with an absorbent secondary dressing if needed.
Chemotherapy-induced peripheral neuropathy
No agent is recommended for preventing CIPN — in particular, avoid acetyl-L-carnitine, which not only lacks preventive benefit but worsened neuropathy in trial data.[9]
Established, painful CIPN duloxetine is the only agent with adequate evidence supporting benefit — start 30 mg/day, increasing to 60 mg/day after about 1 week as tolerated.[9]
When duloxetine is not tolerated or not effective gabapentin, pregabalin, or venlafaxine may be offered, though the evidence supporting them for this specific indication is limited and of lower quality than for duloxetine.
Dose modification remains the single most effective intervention once CIPN meaningfully affects function — dose reduction, a longer interval between cycles, or discontinuation of the causative agent, guided by functional impact (grip, gait, falls) rather than by numeric grade alone.
Extravasation
First step, immediately stop the infusion; do not remove the IV cannula yet — keep it in place to attempt aspiration of residual drug and, if one exists, to give an antidote through it; elevate the affected limb.
Use a pharmacologic antidote whenever one exists for the extravasated drug class — dexrazoxane for anthracycline extravasation, hyaluronidase for paclitaxel or docetaxel extravasation, and sodium thiosulfate for mechlorethamine extravasation.[10]
Apply a thermal compress matched to the extravasated drug class — cold for anthracyclines, antitumor antibiotics, and mechlorethamine; warm for vinca alkaloids, taxanes, and platinums — applied intermittently and continued beyond the first 24 hours rather than for just 1-2 short applications.[10]
Non-Pharmacologic Treatment
- Oral mucositis: soft-bristled toothbrush replaced regularly, gentle flossing (avoid if gums bleed), avoid hard/sharp/spicy/acidic foods, avoid alcohol- and peroxide-containing mouth products.
- Diarrhea: a bland, low-residue, low-fat diet (e.g. bananas, rice, applesauce, toast) during an active episode; adequate oral fluid/electrolyte replacement; avoid caffeine, alcohol, and high-fibre or high-fat foods until resolved.
- Hand-foot syndrome/HFSR: avoid prolonged hot-water exposure, tight or ill-fitting footwear, and repetitive friction/pressure activities (running, manual labour, tight grip tools) on hands and feet.
- Radiation dermatitis: loose, soft clothing over the treatment field; avoid adhesive tape directly on treated skin; use an electric razor rather than a blade if shaving is needed in the field; protect the field from sun exposure during and after treatment.
- Peripheral neuropathy: fall-prevention measures (clear walkways, adequate lighting, supportive footwear); avoid extremes of temperature on hands/feet; use caution with sharp objects and hot surfaces given reduced sensation.
- Infection-prevention hygiene during periods of expected neutropenia: frequent hand hygiene, avoiding large crowds and people with active respiratory illness, avoiding undercooked meat/eggs and unpasteurized dairy, and prompt attention to cuts, burns, or skin breaks.
- Extravasation prevention: careful IV site selection with confirmed blood return before and during a vesicant infusion, and central venous access for high-risk vesicants requiring prolonged infusion.
Special Populations
Pregnancy
Cancer therapy in pregnancy is managed jointly with maternal-fetal medicine and is beyond this chapter's scope, but for the toxicities covered here: bland oral rinses, basic skin care, and topical moisturizers/emollients are compatible with pregnancy. Loperamide and diphenoxylate/atropine are used cautiously and generally reserved for when non-pharmacologic measures are inadequate. Octreotide has limited pregnancy data and should be reserved for genuinely refractory diarrhea after specialist discussion. Duloxetine, gabapentin, pregabalin, and venlafaxine each carry their own pregnancy-specific considerations independent of the CIPN indication — confirm with the treating oncology team before starting any of them in a pregnant patient.
Breastfeeding
Topical products used at standard doses for radiation dermatitis and hand-foot syndrome (moisturizers, low-to-medium-potency topical corticosteroids, topical diclofenac) are generally compatible with breastfeeding given minimal systemic absorption. Loperamide is compatible with breastfeeding. Octreotide and dexrazoxane have limited breastfeeding data; discuss individually with the oncology team.
Pediatrics
This chapter focuses on adult dosing and adult-specific regimens — the loperamide high-dose regimen above, for example, is not a pediatric dose. The same toxicity syndromes occur in children treated for cancer, but doses, some agent choices, and grading nuances differ; consult pediatric oncology-specific dosing resources rather than extrapolating adult doses by simple weight-based scaling.
Older adults
Older adults are at higher risk of dehydration from chemotherapy-induced diarrhea and of falls from both CIPN and gabapentinoid sedation — reinforce fall-prevention counselling explicitly when starting gabapentin, pregabalin, or venlafaxine for CIPN in this group.
Renal impairment
Gabapentin and pregabalin require dose reduction in renal impairment. Octreotide and dexrazoxane should be used cautiously with close monitoring in significant renal impairment. Loperamide does not require renal dose adjustment at standard doses.
Monitoring & Follow-Up
- Oral mucositis: reassess oral intake, pain control, and mucosal appearance at each contact during active treatment; watch for secondary oral candidiasis (persistent white plaques) in a patient with ongoing mucositis, especially if immunosuppressed.
- Diarrhea: track stool frequency/consistency and hydration status; confirm resolution before the next treatment cycle where possible, since ongoing diarrhea affects dosing decisions.
- Hand-foot syndrome/HFSR: examine palms/soles at each visit in a patient on a causative agent; grade severity consistently to guide dose-modification decisions.
- Radiation dermatitis: assess the treatment field weekly during radiation and for several weeks after completion, since peak severity is often reached after treatment ends rather than during it.
- CIPN: reassess sensory/motor symptoms and functional impact (grip, gait, falls) before each cycle of a neurotoxic agent — this, not a fixed cycle count, is what actually drives dose-modification decisions.
- Neutropenia risk: review the neutrophil-count nadir pattern each cycle in patients on myelosuppressive regimens, and confirm the patient knows to seek immediate care for fever rather than waiting for a scheduled visit.
- Extravasation site: reassess at 24-48 hours and again over the following 1-2 weeks for evolving pain, blistering, or skin breakdown, since the full extent of injury can take days to become apparent.
Common Errors to Avoid
- Treating new diarrhea in a cancer patient as automatically chemotherapy-related without considering an infectious cause, especially with fever, recent antibiotics, or bloody stool.
- Using standard OTC loperamide dosing for irinotecan-induced or refractory chemotherapy diarrhea instead of the high-dose regimen this specific situation requires.
- Continuing the high-dose loperamide regimen beyond 48 hours without response instead of escalating to octreotide.
- Using oral cryotherapy or cold foods with an oxaliplatin-containing regimen — cold exposure can trigger oxaliplatin's acute laryngopharyngeal dysesthesia.
- Recommending chlorhexidine mouth rinse or sucralfate for oral mucositis prevention/pain — both were specifically found not to work for this indication despite historical use.
- Recommending aloe vera, honey-based products, or vitamin C/D preparations for radiation dermatitis — current consensus evidence found against all of them despite continued popular use.
- Treating a patient's fever as low priority because they "don't look that sick" — clinical appearance is not a reliable filter in a neutropenic patient; the neutrophil count, not the vital signs alone, defines the emergency.
- Removing the IV cannula immediately after recognizing extravasation — it should stay in place first, to allow aspiration and antidote administration.
- Assuming any topical/oral agent linked from this chapter's Drug Database is available at the exact strength or formulation the evidence describes — confirm the dispensed product's strength (e.g. diclofenac diethylamine gel strength) matches what was actually studied.
- Offering acetyl-L-carnitine to try to prevent CIPN — trial evidence shows it does not prevent neuropathy and may worsen it.
Clinical Decision Algorithm
Drug Tables
How to use this table: doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment and the specific regimen's own dose-modification guide. Select any drug name to open its complete Pharmasist Drug Database page. Antibiotic selection and G-CSF dosing for febrile neutropenia are covered in the companion Infections in the Cancer Patient chapter, not reproduced here.[3]
Oral mucositis
Basic oral hygiene and bland saline/bicarbonate rinses remain first-line for every patient; the agents below are targeted additions.[1]
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Benzydamine oral rinse | Dosing: Rinse/gargle 15 mL for 30 sec-2 min, every 2 h as needed | Numbness, local irritation, nausea, vomiting | None significant | Topical anti-inflammatory/analgesic rinse. Can be diluted with water if it stings. |
| Dexamethasone oral rinse | Dosing: 0.1 mg/mL alcohol-free solution, 10 mL swished 2 min and spat out, 4 times daily, starting day 1 of cycle 1 | Minimal — largely not swallowed | None significant | Prevents everolimus/mTOR-inhibitor stomatitis specifically.[5] Compounded from the injectable solution per institutional recipe — the linked Drug Database entry documents the injectable vial, not a ready-made rinse; confirm the compounding recipe with pharmacy. |
| Doxepin 0.5% oral rinse | Dosing: Institution-specific compounded 0.5% oral rinse — confirm local recipe and volume with pharmacy | Local numbness, unpleasant taste, systemic absorption possible with swallowing | Additive sedation with other CNS depressants | Evidence for pain relief is limited. Not linked: the Drug Database's doxepin monograph documents the oral tablet/capsule antidepressant formulation, not this compounded topical rinse — do not treat that page as dosing guidance for this indication. |
| Morphine (oral) | Dosing: Per current acute-pain dosing guidance, titrated to effect | Sedation, constipation, respiratory depression at high dose | Additive sedation with other CNS depressants; avoid with MAO inhibitors | Systemic option for grade 3-4 mucositis pain preventing oral intake. |
| Hydromorphone (oral) | Dosing: Per current acute-pain dosing guidance, titrated to effect | Sedation, constipation, respiratory depression at high dose | Additive sedation with other CNS depressants | Alternative systemic option for severe mucositis pain. |
| Fluconazole | Dosing: 100-200 mg PO daily for 7-14 days | Headache, nausea, abnormal liver function tests | Numerous CYP2C9/CYP3A4 interactions — screen before starting | For secondary oral candidiasis complicating mucositis, when present. |
| Nystatin (oral suspension) | Dosing: 5-10 mL swish and spit or swallow, 3 times daily | GI upset, unpleasant taste | None significant | First-line for mild secondary oral candidiasis complicating mucositis. |
Not recommended despite historical use: chlorhexidine mouth rinse (does not prevent radiation-associated mucositis) and sucralfate, topical or systemic (does not prevent or treat mucositis pain).[1]
Chemotherapy-induced diarrhea
Distinguish from an infectious cause before treating; see Assessment & Diagnosis.[4]
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Loperamide, standard dose | Adults: 4 mg PO then 2 mg after each unformed stool, maximum 16 mg/24 h | Constipation, dizziness | Avoid with other agents that markedly slow GI motility | Standard OTC dosing for uncomplicated diarrhea. |
| Loperamide, high-dose regimen | Adults: 4 mg PO then 2 mg every 2 h (day) / 4 mg every 4 h (night) until 12 h diarrhea-free, maximum 48 h total | Constipation, dizziness; rare cardiac toxicity reported with supratherapeutic use outside this protocol | Avoid with other agents that markedly slow GI motility | Specific to irinotecan-induced or standard-dose-refractory chemotherapy diarrhea. Do not exceed 48 hours. |
| Diphenoxylate / atropine | Adults: 1 tablet (2.5 mg diphenoxylate) PO 3-4 times daily as needed | Sedation, anticholinergic effects | Additive anticholinergic/sedative effects with other agents | 2nd line when loperamide is not tolerated or not effective. |
| Octreotide | Initial: 100-150 mcg SC 3 times daily Escalation: Up to 500 mcg SC 3 times daily as needed | Hyperglycemia, gallstones, injection-site reactions, fatigue | May alter insulin/oral hypoglycemic requirements | For diarrhea refractory to high-dose loperamide, or complicated diarrhea. Hold chemotherapy and obtain stool studies. |
Hand-foot syndrome and hand-foot skin reaction
Prevention and topical therapy are the same for both entities; dose modification thresholds are grade-based.[6]
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Diclofenac diethylamine gel | Dosing: Apply about 1 g (1 fingertip unit) to palms and soles twice daily, from the start of the causative agent | Local dryness, stickiness, irritation | Avoid in patients with a history of severe NSAID hypersensitivity | Reduces incidence of clinically significant HFS when started with capecitabine.[7] The evidence is for the 1.16% standard-strength product; the linked Drug Database entry documents Voltaren Emulgel Extra Strength (2.32%) — confirm which strength is actually being dispensed before assuming the trial dosing applies unchanged. |
| Pyridoxine (vitamin B6) | Dosing: 150-200 mg/day PO | Peripheral neuropathy with prolonged high-dose use | None significant at these doses | Sometimes prescribed for prevention, but the protective effect is not supported by good-quality evidence. |
| Urea-based emollient/moisturizer | Dosing: Apply to palms/soles at least 3 times daily | Local irritation (uncommon) | None significant | A plain, nonprescription 10-40% urea cream is the product actually used for HFS/HFSR prevention. Not linked: the Drug Database's only urea-containing entry (Emtrix) is a nail-lacquer solution for a different indication, not this generic topical moisturizer. |
Radiation dermatitis
Reflects the current MASCC Delphi-consensus recommendations.[8]
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Mometasone (topical) | Dosing: Apply to the treatment field on radiation treatment days | Local skin atrophy with prolonged use | None significant | Consensus-recommended for prevention. |
| Betamethasone (topical) | Dosing: Apply to the treatment field on radiation treatment days | Local skin atrophy with prolonged use | None significant | Equally consensus-recommended alternative to mometasone for prevention. |
| Hydrocortisone (topical) | Dosing: Apply to the affected field as needed | Local skin atrophy with prolonged use | None significant | Low-potency; for symptom relief of established erythema/pruritus, up to 8 weeks — not the agent used for prevention. |
Not recommended despite historical/traditional use: aloe vera-based products, honey-based products, and vitamin C or vitamin D preparations — current consensus evidence found against all of them.[8]
Chemotherapy-induced peripheral neuropathy
No agent is recommended for prevention.[9]
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Duloxetine | Initial: 30 mg/day PO Titration: Increase to 60 mg/day after about 1 week as tolerated | Nausea, dizziness, fatigue, insomnia | Avoid combining with other serotonergic agents; caution with CYP1A2/CYP2D6 interactions | The only agent with adequate supporting evidence for established, painful CIPN. Do not stop abruptly. |
| Gabapentin | Initial: 200-300 mg/day PO Titration: Increase every 1-7 days by 50-100% of dose as tolerated Maintenance: 300-1200 mg/day PO in divided doses | Dizziness, drowsiness, peripheral edema | Additive CNS depression with other sedating agents | Evidence for this specific indication is limited/of lower quality than for duloxetine. |
| Pregabalin | Initial: 75-150 mg/day PO Titration: Increase every 5-7 days by 50-100% of dose as tolerated Maintenance: 75-300 mg/day PO in divided doses | Dizziness, drowsiness, peripheral edema | Additive CNS depression with other sedating agents | Evidence for this specific indication is limited/of lower quality than for duloxetine. |
| Venlafaxine | Initial: 37.5 mg QHS PO, extended-release Titration: Increase every 5-7 days up to 150 mg/day | Nausea, sleep disturbance, dizziness, dry mouth | Avoid combining with other serotonergic agents | Evidence for this specific indication is limited/of lower quality than for duloxetine. Do not stop abruptly. |
Specifically not recommended for prevention: acetyl-L-carnitine — trial evidence shows it does not prevent CIPN and may worsen it.[9]
Extravasation antidotes
Choose the antidote and thermal-compress direction by extravasated drug class; see Choose Initial Treatment.[10]
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Dexrazoxane | Day 1: 1000 mg/m² IV over 1-2 h Day 2: 1000 mg/m² IV over 1-2 h Day 3: 500 mg/m² IV over 1-2 h | Myelosuppression, injection-site reaction, phlebitis, nausea | None significant at this indication's dosing | Preferred antidote for anthracycline extravasation. Must start within 6 h of the event. |
| Sodium thiosulfate | Dosing: 4 mL of 25% solution diluted with 6 mL sterile water; inject 2 mL of the resulting solution SC around the extravasation area | Local irritation | None significant | Antidote for mechlorethamine extravasation specifically. |
| Dimethyl sulfoxide (DMSO), topical | Dosing: Apply a thin layer topically to the extravasated area, every 8 h for 1 week | Skin irritation, garlic-like odour/taste | None significant | An alternative/adjunct for anthracycline or antitumor-antibiotic extravasation when dexrazoxane is unavailable. |
| Hyaluronidase | Dosing: 150-1500 units diluted in 1 mL normal saline, injected SC/intradermally around the extravasation area, within 1 h of the event | Local irritation | None significant | Antidote for paclitaxel/docetaxel extravasation. Not linked: no standalone Health Canada-marketed hyaluronidase product monograph exists in the Drug Database, and the older standalone brand (Wydase) is no longer marketed in Canada — confirm current local/special-access availability with pharmacy before counting on it being on hand. |
References
- MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy — Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (Elad S, Cheng KKF, Lalla RV, et al.). Cancer 2020;126(19):4423-4431
- Common Terminology Criteria for Adverse Events (CTCAE) — US National Cancer Institute, Cancer Therapy Evaluation Program (CTEP). CTCAE version 6.0 (2025)
- Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update — American Society of Clinical Oncology / Infectious Diseases Society of America (Taplitz RL, Kennedy EB, Bow EJ, et al.). J Clin Oncol 2018;36(14):1443-1453
- Diarrhoea in adult cancer patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up — European Society for Medical Oncology (Bossi P, Antonuzzo A, Cherny NI, et al.). Ann Oncol 2018;29(Suppl 4):iv126-iv142
- Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial — The Lancet Oncology (Rugo HS, Seneviratne L, Beck JT, et al.). Lancet Oncol 2017;18(5):654-662
- Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines — European Society for Medical Oncology (Lacouture ME, Sibaud V, Gerber PA, et al.). Ann Oncol 2021;32(2):157-170
- Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial — Journal of Clinical Oncology (Santhosh A, Sharma A, Bakhshi S, et al.). J Clin Oncol 2024;42(15):1821-1829
- Multinational Association of Supportive Care in Cancer (MASCC) clinical practice guidelines for the prevention and management of acute radiation dermatitis: international Delphi consensus-based recommendations — MASCC Oncodermatology Study Group Radiation Dermatitis Guidelines Working Group (Behroozian T, Bonomo P, Patel P, et al.). Lancet Oncol 2023;24(4):e172-e185
- Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update — American Society of Clinical Oncology (Loprinzi CL, Lacchetti C, Bleeker J, et al.). J Clin Oncol 2020;38(28):3325-3348
- ONS/ASCO Guideline on the Management of Antineoplastic Extravasation — Oncology Nursing Society / American Society of Clinical Oncology (Thomas T, Clark C, Backler C, et al.). JCO Oncol Pract 2026;22(6):924-938 (epub 2025)
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.