Table 5 Studies reporting other non-conventional dosing strategies
From: A systematic review of non-standard dosing of oral anticancer therapies
Publication and country | Aims | Design | Schedule | Reported outcomes | ||
|---|---|---|---|---|---|---|
Efficacy | Toxicity | QoL | ||||
Tanvetyanon et al (2003) US [44] | To describe use of once-weekly imatinib due to cutaneous reactions | Case report, sample = 1, indication: ALL | Dose ranged from 300 mg od to 400 mg once a week, includes dose interruptions Licensed monotherapy starting dose:600 mg od | Nil | Rash, fever, and facial swelling, syncope (with daily dosing, resolved with weekly dosing) | Nil |
Faber et al (2006) US [41] | To investigate safety and efficacy of intermittent dose imatinib following toxicities | Retrospective case series, sample = 12, indication: CML | Standard daily dose on initiation, changed to intermittent dose: range (300-600 mg 1-5 times a week) Licensed monotherapy starting dose:400 mg od | 7 favourable cytogenetic responses (2 complete and 5 major). Improved cytogenetic response in 5 patients, and 1 haematological progression. | Malaise, fatigue, diarrhoea, fluid retention and muscle cramps. | Nil |
Defina et al (2009) Italy [40] | To report tolerability and efficacy of alternate day dosing of lenalidomide | Prospective cohort study, sample = 6, indication: MDS | Lenalidomide 10 mg e.o.d (21/7 plus 7/7 break) Licensed starting dose:10 mg od 21/7 plus 7/7 break | Transfusion independence in all patients within 3-4 months. Cytogenetic response: CR (2) within 6-7 months, PR (3) within 7-9 months. | G3 thrombocytopenia (1), G3 neutropenia (2). | Nil |
Satoh et al (2011) Japan [39] | To compare the efficacy of low-dose gefitinib vs. standard dose | Retrospective cohort sample = 114, indication: EGFR NSCLC | Standard dose group (S1) n = 61: 250 mg od. Reduced dose group (S2), n = 53: 250 mg e.o.d Licensed monotherapy starting dose:250 mg od | Non-inferiority (response and disease control) between groups. Response and disease control rates (83%, 98%) in S2 and (66%, 82%) in S1. Median PFS and 1-year PFS rate: S2 (11.8 months, 50%), S1 (9.9 months, 36%). | Nil | Nil |
Hata et al (2012) Japan [42] | To describe efficacy and toxicity of intermittent erlotinib dosing in 4 cases | Case report, sample = 4, indication: EGFR NSCLC | Various doses used: 150 mg od, 150 mg e.o.d, 200 mg e.o.d, and 100 mg od. Different treatment durations and interruptions Licensed monotherapy starting dose:150 mg od | Responses ranged from partial response to progression. | (1) (2) and (3): G2–3 rash and paronychia resolved with 150 mg e.o.d in cases 1-3. G3 rash resolved with 100 mg od in case 4 | Nil |
Bojic et al (2012) Austria [43] | To report efficacy and toxicity of varying dosages of sunitinib used in 1 case | Case report, sample = 1, indication: metastatic RCC | Schedules used: 4/52 on 2/52 weeks off, continuous therapy, and 2/52 on 1/52 off Licensed monotherapy starting dose:50 mg od 28/7 plus 2/52 break | Different responses from different doses including CR, PR and relapse. | Fatigue and hypertension improved at 37.5 mg od. Improved toxicities and QoL at 2/52 on 1/52 off dosing | QoL improved |
Popat et al (2014) UK [11] | To evaluate efficacy and cost-saving of alternate day dosing of lenalidomide | Prospective cohort study, sample = 39, indication: multiple myeloma | Starting dose 25 mg od for 21/28 followed by 1/52 break. Dose reduced to e.o.d at 25 mg, 15 mg, or 10 mg per dose. Median duration 12 cycles Licensed starting dose:25 mg od 21/7 plus 7/7 break | ORR 85%, CR 3%, VGPR 23%, PR 59%, MR 13%, SD 0%, PD < 1%. Median PFS 11.5 months, Median OS 36.5 months. Cost-savings: £19,408.43/patient | Nil | Nil |
Abdel-Wahab et al (2014) US [45] | To report efficacy and toxicity of intermittent vemurafenib used in 1 case | Case report, sample = 1, indication: BRAF-mutant melanoma | Vemurafenib dose: range 480-960 mg bd, with interruptions due to toxicity. Cobimetinib added at 9 months: dose range 40-60mg od Licensed monotherapy dose:960 mg bd | Marked disease improvement at week 2. Near CR on intermittent schedule. | High WCC, fatigue, anaemia | Nil |
Fukuizumi et al (2015) Japan [46] | To describe management of crizotinib with dose reductions in 1 case | Case report, sample = 1, indication: ALK positive NSCLC | Dose variation: 250 mg bd, 250 mg od, 250 mg every 3 days, and 250 mg bd every 3 days, with dose interruptions. Licensed monotherapy starting dose:250 mg bd | Significant tumor response on escalating to 250 mg bd. Significant response maintained for 13 months with 250 mg bd every 3 days. | Dyspnoea, chest discomfort. | Nil |
Tsukita et al (2015) Japan [47] | To report a case of oesophagitis resolved with alternate day crizotinib | Case report, sample = 1, indication: ALK positive NSCLC | Dose variation: 250 mg bd, 200 mg bd, 200 mg e.o.d, 250 mg bd e.o.d, with interruptions due to toxicity Licensed monotherapy starting dose:250 mg bd | Shrinkage of the spinal metastases then re-growth. | Dysphasia and retrosternal pain, severe oesophagitis, Grade 3 ALT elevation. | Nil |
Saponara et al (2016) Italy [48] | To report four cases treated with low dose imatinib | Case report, sample = 4, indication: GIST | Dose ranges: 800 mg od to 300 mg od, with interruptions Licensed monotherapy starting dose:400 mg od | Responses variable from good to stable disease. | Fatigue, periorbital and leg oedema, and skin toxicities. | Nil |