Study

Method

Participants

Interventions

Outcomes

Notes

Quality

Surgery

Avril (1997, France)

Single centre. Randomisation by sequential sealed envelopes.

ITT

Histologically proven BCCs. Diameter <4cm. T1: 174; T2: 173 patients.

Histological type T1: 79 N, 52 ulcerated, 36 superficial and pagetoid, 7 sclerosing; T2: 74 N, 50 ulcerated, 41 S and pagetoid, 8 sclerosing. Location T1: 53 nose, 36 eyelids, 36 forehead, 10 chin, 5 ear; T2: 49 nose, 42 cheek, 35 eyelids, 29 forehead, 12 chin, 6 ear.

T1: surgery - resection of whole tumour with a free margin of at least 2mm from visible borders. T2: radiotherapy - interstitial brachytherapy, superficial contractherapy, conventional therapy. Chosen by radiotherapist according to tumour parameters, location on face and patient characteristics.

FU: at 3,6,12 months after end of treatment; then yearly until fourth year.

Rate of histologically confirmed persistent tumour or recurrence after 4 years. Patients were examined by dermatologists; photographs of scar taken at 3 standardised distances.

Ex: BCC on scalp or neck. Patients who had total removal of BCC at biopsy, with 5 or more BCCs, life expectancy <3 yrs.

High

Cryotherapy

Hall 1986, UK

Single centre. Method of randomisation not stated

. PP

UK. 105 patients. BP BCCs. Size of lesions: <1cm,1-2cm,>2cm. T1: 44, T2: 49 patients. Sites: T1: 30 neck and face, 6 eyelids, 8 trunk. T2: 40 neck and face, 3 eyelids, 6 trunk.

T1: cryotherapy using a Cry-Owen liquid nitrogen spray gun; all lesions treated with two freeze-thaw cycles, freezing for 1 min each time, with a thaw time of at least 90 s. T2:

Radiotherapy, (130KV X-rays)

FU : Recurrence of tumour and cosmetic appearance at 1, 6, 12, 24 months after treatment. Tumour identified histologically.

12 excluded: 5 died of other causes, 7 lost to follow-up. Ex: recurrent tumours, lesions on nose or pinna, lesion near eye and vision in eye less than 6/18.

Medium

Thissen 2000, Netherlands

Single centre. Method of randomisation not stated. PP

Netherlands. 103 patients. Some BP BCCs. Lesions S or N, < 2cm diameter, localised anywhere on the head and neck.

T1: surgery. T2: cryosurgery (no 3 currette used to debulk the tumour; no 1 used to remove remainder of BCC around the borders, performed under local anesthesia). Freezing: two freezing periods each lasting 20 seconds.

FU: cosmetic and recurrence at 1 year. Recurrence assessed clinically.

Lost to FU:. 3 in control group did not turn up for visits, 1 died (unrelated to treatment), 3 developed recurrent BCC ( all T2)

Medium

PDT

Wang (2001, Sweden)

Single centre. Randomised according to a stratified randomisation pattern in blocks of 10 patients. PP

HP BCC.

44 women; 44 men; age range 42-88years. Type: T1: 22 S, 25 N; T2: 17S, 24N. Distribution 47 trunk, 25 head and neck, 10 legs and 6 arms.Size of lesions not given.

T1: PDT ( 20% weight-based ALA/water in oil cream applied to lesion; irradiation 6 hr later. T2: cryosurgery (two freeze-thaw cycles)

FU: 1,4,8 weeks, 3 months after treatment. Last FU 12 months after first treatment. At three months. Punch biopsy at 3 and 12 months

Ex:BCC on nose; M growth; porphyria; abdominal pain of unknown aetiology; photosensitivity; treatment of BCC with topical steroids type III or IV within the last month.

Loss to FU: T1: 3 , T2:2

Medium

Soler, (2000, Norway)

Single centre. Randomisation numbers in locked envelopes. The patients were randomly allocated on the treatment day to one of the two arms in blocks of four patients. ITT

HP superficial BCC. 83 patients 245 lesions (clinical thickness < 1mm, diameter <3cm)

All lesions in both groups topical 20% ALA, removed after 3 hours and light source applied. T1: laser light (630nm); T2: broadband light.

FU: 3,6 months after treatment. Outcomes : complete, partial or no response; cosmetic outcome and pain intensity during treatment and FU

High

INF alpha

Alpsoy, (1996, Turkey)

Single centre. Method of randomisation not stated. ITT

45 patients. HP BCC. T1: 15, T2: 15, T3: 15 patients. Mean age T1: 58.7 yrs, T2: 63.6 yrs, T3: 60.3 yrs. Histological types T1:12N, 1S, 2MOR; T2: 11N, 2S, 2 MOR; T3: 11N, 2S, 2 MOR. Lesion size (median) T1:2.05cm2;T2:1.82 cm2;T3: 1.9cm2.

T1: INF alfa-2a; T2: INF alfa 2b; T3: INF alfa 2a and 2b..

FU: cytologic specimens taken at 8 weeks after completion of therapy; all cases evaluated clinically and histologically.

Ex: Recurrent lesions, genetic or nevoid conditons, deep tissue involvement.

Medium

Cornell (1990, USA)

Multi-centre (4). Randomisation by computer generated. PP

. T1: 123, T2: 42 patients. BP BCCs. Mean age T1: 56 yrs, T2: 57 yrs. Histological type T1: 57 S, 66 N ulcerative; T2: 19S, 23 N. Mean lesion area T1:83mm ², T2: 75mm ².

T1: Intralesional injections 1.5 million IU of IFN alfa-2b; T2: vehicle for IFN preparation

3 alternate days/week for 3 consecutive weeks.

FU: weekly after each of the 3 treatments then at 5, 9, 13 weeks after completion of treatment, then every 3 months to 52 weeks.

Ex: Previously received therapy to test site, immunosuppressive or cytotoxic therapy (within prior 4 weeks), or exogenous IFN/IFN alfa-2b (Intron A), debilitating illness, high risk areas. Loss to FU: 7 patients all in T1 due to missed injections and adverse experiences.

Medium

Edwards, (1990, USA)

Single centre. Method of randomisation not stated. PP

T1: 33, T2:32. BP BCC. Age range 35-65 years. Histological type: T1:16S , 17N; T2:15S,15N. Lesions ranging in size form 0.5-1.5 cm for nBCC or 2cm for sBCC

10 million IU zinc chelate interferon alfa-2b: T1: single injection; T2: one dose per week for 3 weeks

BCC measured, photographed before each treatment and at beginning of the 2nd, 8th, 12th and 16th week after the first injection. Biopsy at week 16.

Ex: thromboembolic disease, radiation therapy to the test site area, history of arsenic ingestion, pregnancy, immunosuppression, receiving NSAID, MOR BCC, recurrent cancers, deeply invasive lesions, periorificial tumours, central facial BCC. Loss to FU: 2 in T2 due to flulike symptoms

Medium

INF beta

Rogozinski, (1997, Poland)

Single centre. Method of randomisation not stated. ITT

T1: 17, T2: 18 patients.

T1: recombinant INF-beta, T2: placebo.

FU: 16 weeks after treatment and 2 years.

Medium

5-FU

Romagosa 2000 (USA)

Single centre, Method of randomisation not stated. ITT

13 patients, 17 BP non-s BCCs which measures at least 0.7 cm in greatest diameter

T1: 5% 5-FU in PC vehicle, T2: 5% 5-FU in a petrolatum base. T1 and T2 Applied am and pm for 4 consecutive weeks

FU: every 4 weeks for 16 weeks. Final visit was biopsy at site.

Ex: systemic disease, women of childbearing age, facial BCCs.

Medium

Miller 1997 (USA)

Multicentre, randomised, open-label Method of randomisation not stated. PP

97 males, 25 female. Single BP BCC. Mean age 61 years. Histological type: 38 S , 85 N. Location: 9 head, 9 neck, 38 upper extremities, 11 lower extremities, 55 trunk. Lesion area median 80 mm2.

6 treatment regimens with 5-FU/epi gel:. T1: 1.0 ml once weekly for 6 weeks; T2: 0.5 ml once weekly for 6 weeks; T3: 1.0 ml twice weekly for 3 weeks; T4: 0.5ml twice weekly for 3 weeks; T5: 0.5 ml twice weekly for 4 weeks; T6: 0.5 ml three times weekly for 2 weeks.

FU examinations of patients at 1,4,8,12 weeks after last injection. At each visit patient and investigator gave subjective evaluation of cosmetic appearance of lesion.

Ex: high risk sites. Lesions with deep tissue involvement, basal cell nevus syndrome, hypersensitivities or allergies to 5-FU, sulfites, epinephrine, bovine collagen, history of autoimmune disease, pregnancy. Six patients were lost to follow-up

Medium

Imiquimod

Beutner, (1999, USA)

Single centre. Randomisation to give 2:1 ratio of imiquimod cream to vehicle cream. Method of randomisation not stated. ITT

Age range 37-81 years.

BP BCCs: T1: 7, T2: 4 , T3: 4, T5: 5, T6: 11 patients. Size 0.5-2 cm2. Main upper body. Histological type: T1: 1N, 2S; T2: 1 N, 3S; T3: 4S; T4: 2N, 3S; T5: 2N, 2S; T6: 1N, 10S.

Imiquimod 5% cream: T1: twice/day; T2: once/day; T3: three times/week; T4: twice/week; T5: once/week; T6: vehicle.

FU: 6 weeks after treatment tumour site excised and examined histologically.

Medium

Marks, (2001, Australia and New Zealand)

Multicentre.

Method of randomisation not stated. ITT

72 male, 27 female. HP BCC; surface area 0.5-2 cm². Location: 32% upper limbs, 28% trunk, 40% head & neck.

5% imiquimod: T1: twice/day, T2: once/day, T3: twice/day for 3 days each week, T4: once/day for 2 days each week.

FU: 1,2,4,6 weeks. Excision at week 6. Lost to FU: T2: 2 (pruritus), T3: 1 (CVA), T4: 1 (excision of nearby tumour).

Medium

Geisse, (2001, USA)

Multicentre, randomised, blinded, vehicle-controlled dose response study. Method of randomisation not stated. ITT

N=128

Single, primary, BP S BCC (0. 5-2.0 cm²)

Imiquimod for 12 weeks: T1: twice daily, T2: once daily, T3: Mon- Fri, T4: Mon,Wed,Fri

FU: surgical excision 6 weeks after treatment.

Medium

Sterry a (2001, USA)

Multicentre, randomised open-label, dose response. Method of randomisation stated. ITT

93 patients, single, primary, BP S BCC (0.5-2 cm²)

T1/T2: imiquimod 3 times/week for 6 weeks with occlusion T1, and without occlusion T2. T3/T4: imiquimod twice a week for 6 weeks with occlusion T3 and without T4

FU: surgical excision 6 weeks after treatment

High

Sterry b (2001, USA)

Multicentre, randomised open-label, dose response. Method of randomisation stated. ITT

90 patients, single, primary, BP N BCC (0.25-1.5 cm²)

T1/T2: imiquimod 3 times/week for 6 weeks with occlusion T1, and without occlusion T2. T3/T4: imiquimod twice a week for 6 weeks with occlusion T3 and without T4

FU: surgical excision 6 weeks after treatment

High

Shumack, (2001, USA)

Multicentre, randomised, open label, dose-response study. Method of randomisation not stated. ITT

99 patients, single, primary, BP nBCC

( 0.5-1.5cm²)

Imiquimod for 6 weeks. T1: twice daily, T2: once daily, T3: twice daily 3 days/week, T4: 3/week.

FU: surgical excision 6 weeks after treatment.

Medium

Robinson, (2001,USA)

Multicentre, randomised, blinded, vehicle-controlled dose response study. Method of randomisation not stated. ITT

92 patients, single, primary, BP N BCC (0.5 to 1.5cm²)

Imiquimod for 12 weeks: T1: twice daily, T2: once daily, T3: (Monday-Friday) T4:, Mon- Wed-Fri

FU: surgical excision 6 weeks after treatment.

Medium