Patient-reported preferences for oral versus intravenous administration for the treatment of cancer: a review of the literature

Figures & data

Table 1 Data extraction table

Reference, study design	Study sample	Study results/analysis of predictors	Other considerations
Beusterien et al^Citation14 • Online survey • Conjoint analysis	N=102 adult female patients with breast cancer (any stage) currently receiving neo/adjuvant or palliative chemotherapy Age (mean): 54 years, SD=11 Line of chemotherapy: • Adjuvant treatment group (mean): 1.8, SD=0.65 • Palliative treatment group: 2.8, SD=1.3 • Cancer stages: 1 (n=10, 10%), 2 (n=34, 34%), 3 (n=29, 28%), 4 (n=29, 28%)	Support for oral Most preferred mode of administration: 21-day cycle of oral tablets taken twice daily for 2 weeks Least preferred mode of administration: 21-day cycle of 3-hour infusions administered on three separate days Analysis of predictors: none	Toxicity: type and grade of toxicity associated with a treatment was found to be important for driving preference For example, patients were accepting of increased risk of lower grade toxicities (eg, alopecia) when associated with a more convenient mode of administration (oral), but preferred a less convenient regimen if it led to a lower risk of severe toxicities (eg, motor neuropathy)
Borner et al^Citation23 • Randomized cross-over trial where patients were randomized to either oral or IV chemotherapy for the first treatment cycle, and switched to IV for the second cycle • Oral chemotherapy taken daily for 28 days every 5 weeks. IV chemotherapy administered for 5 days every 4 weeks • Patients completed a Therapy Preference Questionnaire before first treatment cycle and after second treatment cycle	Total N=36 Sample initially randomized to “oral chemotherapy” (n=19): female: n=5, 26.3%; male: n=14, 73.7%; age (median): 58 years (range: 33–73) Prior treatment for malignancy within “oral group”: surgery: 18 (95%); radiotherapy: 2 (16%); adjuvant chemotherapy: 6 (32%) Sample initially randomized to “IV chemotherapy” (n=17): female: n=4, 23.5%; male: n=13, 76.5%; age (median): 60 years (range: 39–82) Prior treatment for malignancy within IV group: surgery: 16 (94%); radiotherapy: 2 (12%); adjuvant chemotherapy: 4 (24%)	Support for oral Of the 31 patients who completed the study, 84% (n=26) preferred oral chemotherapy to IV Mean strength of preference for each treatment on a 1–5 scale, where 1= no preference and 5= strong preference, was 4.12 for oral and 3.40 for IV Analysis of predictors: treatment sequence; treatment sequence did not affect whether patients preferred oral or IV treatment. Specifically, after having received both types of treatment, 88% of patients who were randomized to receive oral chemotherapy first preferred oral over IV and of the patients randomized to receive IV treatment first, 79% of patients preferred oral treatment. Therefore, preference for oral over IV chemotherapy was high in both groups	Side effects: prior to undergoing treatment, side effects (specifically risk of infection, vomiting, and diarrhea) were rated as the top three factors associated with treatment preference. After treatment, side effects were rated as the second and third factors, following the ability to receive treatment at home Oral chemotherapy was associated with more diarrhea, but equivalent nausea and vomiting, as compared to the IV treatment, whereas the IV treatment was associated with significantly more stomatitis and hematological toxicity Patients who preferred IV treatment (n=5) had higher incidences of diarrhea, nausea, and vomiting Ability to receive treatment at home: prior to receiving treatment, taking the medication at home was rated as the fourth attribute associated with treatment preference, whereas after completing treatment it was rated first
Calhoun and Roland^Citation21 • Survey study	N=39 adult female patients with ovarian cancer who have undergone first-line IV treatment	Support for oral Of the 39 patients surveyed, 56% preferred oral chemotherapy, 28% preferred IV chemotherapy, and 15% did not have a preference Attributes for oral: convenience, efficacy Analysis of predictors: none	None
DiBonaventura et al^Citation25 • Qualitative interviews; cross-sectional survey; choice-based conjoint exercise	N=181 adult female patients with metastatic breast cancer Age (mean): 52 years, SD=9 Ninety percent of patients were currently receiving treatment, most commonly, hormone therapy (47.5%), IV chemotherapy (42%), and oral chemotherapy (24.3%) All patients had previous experience with IV chemotherapy and half (52.5%) had received oral chemotherapy	Support for oral or IV not reported Analysis of predictors: previous treatment experience: patient preference did not vary by number of rounds of chemotherapy Factors most strongly related to treatment preference: survival of 3 months and a 0% risk of fatigue and alopecia	Adherence: forgetting to take medications and/or keep treatment appointments was the most frequently reported reason for treatment non-adherence (n=26, 41.3%) among the 34.8% (n=63) of subjects who had discontinued or were non-adherent to their treatment Toxicity was the second most common reason for treatment non-adherence (n=23, 36.5%)
Fallowfield et al^Citation15 • Qualitative interviews	N=79 adult female patients with metastatic breast cancer who were newly prescribed oral (n=35) or IV (n=44) bisphosphonate treatment for bone metastases Age (mean): oral: 62, SD=12; IV: 63, SD=13	Support for oral Mean patient satisfaction for treatments: oral =59%; IV =41% Attributes against oral: time required to stand upright, inability to eat or drink Analysis of predictors: none	Dosing schedule: daily for oral, monthly for IV Adherence: 18% (n=6) rarely forgot to take their oral treatment and 21% (n=7) chose to stop taking treatment compared to n=3 who missed an IV treatment Reasons for non-adherence (oral treatment): inconvenience when not at home and the desire to eat or drink before taking the medication
Gornas and Szczylik^Citation16 \• Observational study questionnaire	N=281 adult female patients with metastatic breast cancer (n=215 completed the preference questionnaire) Age range: 27–77 years Number of lines of prior chemotherapy: 0 (n=38, 17%), first line (n=85, 39%), second line (n=65, 30%), third line (n=22, 10%), fourth line (n=7, 3%), fifth line (n=1, 1%) Number of metastatic sites: 1 (n=57, 26%), 2 (n=92, 42%), 3 (n=55, 25%), 4 (n=14, 6%)	Support for oral Patient preference for oral by line of treatment (1, 2, and 3): Convenience: 52%, 73%, and 72% Ability to stay home during treatment: 65%, 74%, and 56% Attributes for oral: convenience, ability to stay home during treatment, desire to continue working, no contraindications Analysis of predictors: ability to stay at home. Of the 71 patients who provided only one reason for preferring oral to IV treatment, 30 patients (42%) reported the ability to stay home Reason for choosing oral treatment by line of treatment: First line (n=38), convenience (52%); ability to stay home (65%). Second line (n=85), convenience (73%), ability to stay home (74%). Third line (n=95), convenience (72%), ability to stay home (56%)
Ishitobi et al^Citation17 • Postoperative patients attending follow-up visits at a cancer center were asked to complete a questionnaire \regarding their preference between oral and IV treatment	N=82 postmenopausal adult female patients with early ER+ HER2− breast cancer and who had been previously treated with adjuvant chemotherapy. Patients with evidence of recurrence and those who had previously received neoadjuvant chemotherapy were excluded. Age range: 50–79 years Previous treatment: oral chemotherapy (n=11, 13%), IV chemotherapy (n=71, 87%). No patients had received both treatments	Support for oral Preferred oral to IV 45% versus 35% (20% no preference); all patients who previously received oral treatment preferred oral (n=11, 100%); of the patients who had previously received IV treatment, 41% preferred IV, 37% preferred oral, and 23% had no preference Attributes for oral: place of treatment, anxiety over IV treatment Attributes for IV: treatment duration, efficacy Analysis of predictors: none	Toxicity: dose reduction and/or early cessation of adjuvant chemotherapy as a result of adverse event was not significant between oral (9%) and IV (21%) groups Preference and well-being: patients who received the treatment type they preferred (oral or IV) reported significantly better psychological status (as measured on a 5-point Likert scale, 1= very bad, 5= very good) during chemotherapy compared to those patients who preferred oral treatment and received IV therapy Efficacy: although the treatments were presented as equally effective, patients who preferred IV treatment regarded it to be more effective than oral treatment
Liu et al^Citation8 • Structured survey on medication administration preferences	N=103 adult patients with incurable cancer likely to receive palliative chemotherapy in the future Female: n=59, 57.3%; Male: n=44, 42.7% Age (mean): 63 years (range: 33–89 years) Primary diagnosis: lymphoma (n=40), breast (n=35), other (n=15), colorectal (n=8), gynecologic (n=8), lung (n=5) Previous treatment: IV chemotherapy (n=41), no chemotherapy experience (n=47), oral chemotherapy (n=9), both oral and IV chemotherapy (n=6)	Support for oral 89.3% preferred oral medication; patients unwilling to stay on oral if IV had higher efficacy Attributes for oral: convenience, problems with IV access and needles, environment (can take medication at home), travel, previous IV issues Attributes against oral: forgetting to take oral meds Attributes for IV: someone else can administer, 1-day treatment Differences by demographic factors: no significant differences in preference were found based on previous chemotherapy experience, age, sex, or type of cancer, although differences in attributes associated with preference were found (discussed as follows) Age and sex: women were more worried about IV issues than men, which the authors speculate may be due to having smaller and less accessible veins Convenience was more important to younger men than to any other age cohort, and was significantly more important to younger men than to older women. Convenience was more important to younger men than any other group	Efficacy: nearly three-quarters of patients were not willing to trade any level of treatment efficacy to receive treatment via their preferred mode of administration (70% unwilling to sacrifice response rate, 74% unwilling to sacrifice duration of response) Adherence: four patients stated often forgetting to take their oral medication, and ten patients worried about their adherence Decision-making: patient preference for physician to decide the mode administration (39%), preference for the decision to be made jointly (23%), preference for the patient to make the decision for themselves (38%). Women 65 years and older were 3.5 times more likely to prefer that their physician make this decision than men younger than 65 years (57% versus 15%) All 31 of the 33 patients who listed poor previous experience with IV who preferred oral treatment also listed at least a second reason for their choice. Two of these 31 patients preferred IV regardless of past experience
Mahner et al^Citation6 • Patients chose oral or IV treatment at the start of the study. Four patients (4%) did not select their treatment mode of administration prior to the study and were randomized to receive IV (n=3 patients) or oral treatment (n=1 patient)	N=102 adult female patients with platinum-resistant or refractory ovarian cancer Age (median): 72 years (range 65–87) Median number of prior chemotherapy regimens =3 (range: 1–6)	Support for IV 84 patients (82%) selected IV treatment; 14 patients (14%) selected oral Analysis of predictors: none	None
Peeters et al^Citation18 • Pilot survey regarding oncology patients’ preferences for maintenance therapies • Preference was assessed at start of chemotherapy (T0), after two cycles (T1), and after four cycles (T2)	N=30 adult patients with stage 5 non-small cell lung cancer scheduled to begin first-line platinum-based doublet chemotherapy Female: n=13, 43.3%; male: n=17, 57.0%; age (median): 66 (range: 32–79) Disease control was achieved in 60% of patients after four cycles of chemotherapy	Support for oral Both oral and IV were acceptable; 90% preferred oral; IV acceptability increased with additional courses of chemo Attributes for IV: experience with IV Analysis of predictors: efficacy; patients appear to favor MT as long as survival expectations are several months (83%, 67%, and 43% of patients agreed MT was worthwhile when associated with survival of 6, 3, or 1 months, although support decreased with additional lines of chemotherapy) Symptom relief: similarly, support for symptom relief and tumor control (with no associated survival benefit) were important to patients (eg, about 90% of patients at T0), but this decreased with additional lines of chemotherapy	Side effects: three-quarters of patients stated they would tolerate mild or moderate toxicity with MT The authors argue that prolonged symptom control is important to non-small cell lung cancer patients given that less than one-fifth would choose a treatment associated with a survival of 3 months, but almost 70% stated they would opt for a treatment that improved their quality of life even without survival benefit
Pfeiffer et al^Citation24 • Patients were randomized to either oral or IV treatment, then crossed over to the alternative mode of administration. After receiving both modes of administrations patients selected one mode to receive for an additional 12 weeks of treatment • The Therapy Preference Questionnaire developed by Borner et al^Citation9 was administered to patients prior to the start of treatment, after completing treatment with both modes of administration, and after selecting a treatment to receive for 12 additional weeks	N=60 adult patients with histologically proven adenocarcinoma of the colon or rectum Sample initially randomized to oral chemotherapy: female: n=14 (46.7%); male: n=16 (53.3%); age (median): 63 years (range: 45–79 years); adjuvant therapy: 26 (86.7%); palliative therapy: 4 (13.3%) Sample initially randomized to IV chemotherapy: female: n=15 (50.0%); male: n=15 (50.0%); age (median): 69 years (range: 36–81 years); adjuvant therapy: 27 (90.0%); palliative therapy: 3 (10.0%)	Support for IV Of the 49 patients evaluated that completed the study, 30 (61%) preferred IV chemotherapy and opted to receive this mode of administration for an additional 12 weeks, whereas oral chemotherapy was preferred and continued by 19 (39%) patients Following 12 weeks of additional treatment with the mode of administration selected by the patients, four patients stated that they would have preferred to receive the other mode, specifically, n=3 would have chosen oral and n=1 would have chosen IV Median strength of preference was rated high for both modes of administration (grade 4 or 5) Attributes for IV: side effects (less diarrhea, nausea, tiredness); less interference with daily activities Attributes for oral: preference for pills; preference for taking medication at home Analysis of predictors: treatment sequence; a greater percentage (46%) of patients who were randomized to receive oral treatment first preferred oral treatment over IV, whereas 30% of patients treated with IV first preferred oral treatment	Side effects: side effects were ranked as the top three factors associated with preference prior to treatment, specifically risk of infection, vomiting, and diarrhea In the group of patients receiving IV then oral treatment, two cases of grade 3 toxicity were reported with IV treatment compared to eleven cases with oral. As oral treatment was associated with greater side effects and preferred less by patients than IV, the authors concluded that side effects are more important to patients’ treatment preferences than location of treatment administration (home or hospital)
Schott et al^Citation22 • Survey of treatment preferences for patients currently receiving oral or IV chemotherapy	N=224 adult female patients with histologically confirmed breast cancer currently receiving IV or oral chemotherapy Sample receiving oral chemotherapy (n=60): age (mean): 55.8 (range: 26–81) Current treatment: neoadjuvant: 0; adjuvant: 0; palliative: 60 (100%) Prior experience with oral chemotherapy: 12 (20%) Sample receiving IV chemotherapy (n=164): age (mean): 52.6 (range: 30–76) Current treatment: neoadjuvant: 10 (6.1%); adjuvant: 95 (57.9%); palliative: 59 (36.0) Prior experience with oral chemotherapy: 20 (12.2%)	Support for oral If given the choice between two equally effective oral or IV chemotherapy treatments, 89.3% of women treated with oral chemotherapy would choose this treatment again compared to 67.1% of patients treated with IV chemotherapy Attributes for oral: personal benefit; less impact on daily/family life; easier to cope with disease; autonomy; less side effects Attributes against IV: everyday life affected by hospital visits to receive treatment Mode of administration received: significantly more patients receiving oral treatment compared to patients receiving IV treatment reported agreement with following statements regarding oral mode of administration:  It provides personal benefit to the patient  It has less impact on patients’ daily life and families  It makes it easier to cope with disease  It makes it easier to handle one’s disease by providing patients with more autonomy administration  It makes patients feel less ill than IV treatment  It has less side effects than IV treatment  It is as effective as IV chemotherapy There were no significant differences between oral and IV-treated patients in terms of their fear of taking oral medication incorrectly, and no significant differences based on age (50 years and older versus younger than 50 years) Moderately strong significant correlations were identified amongst several survey questions, the strongest being the correlation between strongly agreeing that oral chemotherapy could help patients to better cope with their disease and the belief that oral chemotherapy provides patients with more autonomy	Perceptions of oral chemotherapy: most of the overall sample (50% or more of patients receiving both oral and IV chemotherapy) reported strongly agreeing or agreeing with the following: • There is a personal benefit to receiving oral versus IV chemotherapy • Everyday life is affected by hospital trips in order to receive IV chemotherapy • Oral chemotherapy affects daily life/family less than IV chemotherapy • Oral chemotherapy makes it easier to handle one’s disease by providing patients with more autonomy outside of the clinic • Oral chemotherapy is as effective as IV Overall, most patients did not believe that an oral chemotherapy treatment would make it easier to cope with their disease; that it would make them less ill or have less side effects than IV treatment; and did not report fear of taking oral medication incorrectly
Seaman et al^Citation19 • Semi-structured interviews assessing cancer-associated thrombosis patients’ understanding of their condition and treatment	N=14 adult patients with active advanced cancer receiving LMWH for at least three consecutive months to treat venous thromboembolism Female: n=8 (57.1%); male: n=6 (43.0%); age (mean): 66 (range: 52–84) Primary cancer type: breast (n=3), ovarian (n=3), colorectal (n=2), bowel (n=1), cholangiocarcinoma (n=1), colon (n=1), lung (n=1), renal cell (n=1), stomach (n=1) Sites of metastases (not mutually exclusive): bone (n=3), cervical nodes (n=1), liver (n=2), lung (n=2), lymph nodes (n=2), mesenteric nodes (n=1), soft tissue metastases (n=1) Stage: IV (n=10), IIIc (n=2), locally advanced with lymph node involvement (n=1), unknown (n=1)	Support for oral Majority of patients hypothetically preferred oral treatment; all valued efficacy over convenience and reported daily IV treatment was an acceptable “necessary evil” Attributes for IV: ability to treat illness Attributes against IV: side effects Analysis of predictors: none	Efficacy: patients preferred a more effective injection over a more convenient oral medication Adherence: only one participant reported missing a dose of LMWH
Teuffel et al^Citation20 • Patient interviews assessing mode of administration (oral versus IV) preference in four hypothetical settings	N=78 adult patients with FN receiving treatment for cancer Female: n=46 (59.0%); male: n=32 (41.0%); age (mean): 54 (range: 20–88) Cancer type: genital (n=21, 26.9%), gastrointestinal (n=17, 21.8%), leukemia (n=14, 17.9%), lymphoma (n=7, 9.0%), breast (n=7, 9.0%), other (n=6, 7.7%), multiple myeloma (n=3, 3.8%), lung (n=3, 3.8%)	Support for oral 75% preferred an outpatient setting; 36% of patients preferred oral administration, and 21% preferred IV administration Analysis of predictors: differences by demographic factors: demographic (age, sex, marital status, education level, employment status, health benefit plan, income, travel time to hospital) and disease-specific factors (history of FN; diagnosis of leukemia, lymphoma, or myeloma; relapsed disease; quality of life) were not significantly related to treatment preference	None

Abbreviations: IV, intravenous; SD, standard deviation; ER+, estrogen receptor-positive; HER2−, human epidermal growth factor receptor 2-negative; LMWH, low-molecular-weight heparin; FN, febrile neutropenia; MT, maintenance therapy.

Table 2 Positive attributes associated with oral administration reported by patients with cancer

Attribute	Description of attribute	Study sample
Able to take at home^Citation8,Citation16,Citation24	Ability to receive treatment at home	Patients with metastatic breast cancer;^Citation16 patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer;^Citation8 patients with colorectal cancer^Citation24
Convenience^Citation8,Citation16,Citation21	Treatment regarded as a more convenient way of taking medication	Patients with metastatic breast cancer;^Citation16 patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer;^Citation8 patients with ovarian cancer^Citation21
Desire to continue working^Citation16	Desire to continue one’s job during treatment	Patients with metastatic breast cancer
No contraindications^Citation16	The lack of contraindications associated with IV or combined treatment	Patients with metastatic breast cancer
Previous issues with IV treatment^Citation8	Description of attribute not reported	Patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer
Problems with IV access and needles^Citation8	Issues such as “pain and difficulty starting an IV line”	Patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer
Travel^Citation8	Description of attribute not reported	Patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer
Place of treatment^Citation17	Description of attribute not reported	Postmenopausal patients with early ER+/HER2− breast cancer
Efficacy^Citation21	Perception that oral mode of administration for treatment was efficacious	Patients with ovarian cancer
Personal benefit^Citation22	Description of attribute not reported	Patients with breast cancer
Impact on daily life and relationships^Citation22	Oral chemotherapy has less of impact on one’s daily life and family than IV treatment	Patients with breast cancer
Coping^Citation22	Oral chemotherapy makes it easier to cope with one’s disease	Patients with breast cancer
Autonomy^Citation22	Oral chemotherapy makes it easier to handle the disease by providing patients with more autonomy outside the clinic	Patients with breast cancer
Side effects^Citation22	Oral chemotherapy perceived to have fewer side effects and to make patients less ill compared to IV treatment	Patients with breast cancer
Mode of administration^Citation24	Preference for treatment in pill form	Patients with colorectal cancer

Abbreviations: IV, intravenous; ER+, estrogen receptor-positive; HER2−, human epidermal growth factor receptor 2-negative.

Table 3 Negative attributes associated with oral administration reported by patients with cancer

Attribute	Description of attribute	Study sample
Time required to stand upright^Citation15	Refers to oral bisphosphonate treatment, where patients must remain upright for at least 30 minutes to limit epigastric pain	Patients with metastatic breast cancer being treated for bone metastases with bisphosphonates
Inability to eat or drink^Citation15	Refers to oral bisphosphonate treatment, which must be taken in the morning on an empty stomach; patients reporting wanting to drink or eat beforehand as a reason for non-adherence	Patients with metastatic breast cancer being treated for bone metastases with bisphosphonates
Forgetfulness^Citation8	Easy to forget to take oral medication	Patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer

Table 4 Positive attributes associated with IV administration reported by patients with cancer

Attribute	Description of attribute	Study sample
Efficacy^Citation8	Perception that IV treatment is more effective than oral	Patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer
Someone else can administer^Citation8	Preference for treatment that one does not have to worry about administering to oneself	Patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer
Experience with IV^Citation18	Refers to greater acceptance of IV treatment after previously undergoing chemotherapy	Patients with stage 5 non-small cell lung cancer
Ability to treat illness^Citation19	Perception that IV treatment helped to keep one’s disease under control	Patients with cancer-associated venous thromboembolism, with the following primary cancer type: breast, ovarian, colorectal, bowel, cholangiocarcinoma, colon, lung, renal cell, and stomach
Treatment schedule^Citation8,Citation17	Preference for treatment that can be administered in 1 day or for a shorter duration of time	Postmenopausal patients with early ER+/HER2− breast cancer and who had been previously treated with adjuvant chemotherapy;^Citation17 patients with a primary diagnosis of lymphoma, breast, colorectal, gynecologic, lung, or other cancer^Citation8
Interference with daily activities^Citation24	Perception that IV treatment interferes less with one’s daily life	Patients with colorectal cancer

Abbreviations: IV, intravenous; ER+, estrogen receptor-positive; HER2−, human epidermal growth factor receptor 2-negative.

Table 5 Negative attributes associated with IV administration reported by patients with cancer

Attribute	Description of attribute	Study sample
Side effects^Citation19,Citation24	Patients reported side effects associated with treatment that impacted their daily lives (eg, severe shortness of breath, diarrhea, vomiting, tiredness)	Patients with stage 5 non-small cell lung cancer;^Citation19 patients with colorectal cancer^Citation24
Impact on daily life^Citation22	Everyday life affected by hospital visits to receive IV treatment	Patients with breast cancer

Abbreviation: IV, intravenous.

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