Table 1 Characteristics of the included studies assessing the response to temozolomide-based chemotherapeutic regimens in patients with pNET

Kulke et al. (a) 2006, US [23]

Single arm trial

Patients with locally unresectable or metastatic pNET

TMZ (150mg/m2 for 7 days every other week), and thalidomide (50-400mg daily)

11

56 (28-78)^a

62^a

45^a

NE

Kulke et al. (b) 2006, US [24]

Single arm trial

Patients with advanced pNET

TMZ (150 mg/m2 for 7 days), and bevacizumab (5 mg/kg) every other week

17

61 (37-75)^a

56^a

35^a

Not reported

Chan et al. (a) 2012, US [25]

Single arm trial

Patients with locally unresectable or metastatic pNET

TMZ (150mg/m2 for 7 days), and bevacizumab (5mg/kg on days 1) every other week

15

60 (36-74)^a

56^a

21^a

14.3 (8.5- NE)

Chan et al. (b) 2013, US [26]

Single arm trial

Patients with low or intermediate grade locally unresectable or metastatic pNET

TMZ (150mg/m2 for 7 days every other week), and everolimus (5-10m per day)

40

53 (28-87)

60

23

15.4 (9.4-20.4)

Fine et al. 2014, US [27]

NCT00869050

Single arm trial

Patients with progressive, differentiated, metastatic pNET

TMZ (150-200mg/m2 on days 10-14), and capecitabine (1500/m2 on days 1-14) each 4 weeks

11

30-89

39^a

Not reported

 > 18.2

Claringbold et al. 2016, Australia [28]

Single arm trial

Patients with low or intermediate grade locally unresectable or metastatic pNET

Capecitabine (1500mg/m2 for 14 days), TMZ (200mg/m2 in the last 5 days of capecitabine) both commenced 5 days before 177Lu-octreotate each 8 weeks

30

60 (38-78)

60

13

48

Pavel et al. 2018, Germany [29]

NCT02231762

Single arm trial

Patients with low or intermediate grade unresectable, progressive pNET

TMZ (150 mg/m2 for 5 days in the first month, and 200 mg/m2 in the next months), and lanreotide Autogel (120mg) each 4 weeks

16

63.1 (± 11.0)^a

58^a

Not reported

11.1 (8.3-NE)

Cheng et al. 2018, China [30]

Parallel non-randomized trial

Patients with well-differentiated locally advanced or metastatic pNET

TMZ (150-200mg/m2 on days 1-7), and Endostar (15mg on days 1-14) each 3 weeks

6

48 (37–71)

57

7

12 (0.0-30.1)

Dacarbazine (250mg on days 1-5), 5-FU (500mg on days 1-5), and Endostar (15mg on days 1-14) each 3 weeks

8

Bhave et al. 2018, US [31]

NCT01465659

Single arm trial

Patients with locally unresectable well differentiated pNET

TMZ (75-150mg/m2 for 7 days every other week), and pazopanib (400mg daily)

26

Above 18

52

Not reported

12.1 (5.7–25.1)

Kobayashi et al. 2021, Japan [32]

Single arm trial

Patients with locally unresectable or metastatic pNET

TMZ (200 mg/m2 on days 1-5) each 4 weeks

3

65 (40-75)^a

46^a

100

2

Shaheen et al., US NCT01525082 [33]

Single arm trial

Patients with low or intermediate grade locally unresectable or metastatic pNET

TMZ (on days 10-14), capecitabine (on days 1-14), and bevacizumab (on days 1 and 15) each 4 weeks

19

53.9 (± 10.7)

55

Not reported

Mean: 25.2 (18.7- 31.7)

Pavlakis et al. Austria [34, 35]

NCT02358356

Randomized clinical trial

Patients with low or intermediate grade locally unresectable or metastatic pNET

TMZ (150mg/m2 on days 10-14), and capecitabine (1500mg/m2 on days 10-14) each 4 weeks

9

NR

NR

Not reported

Not reported

TMZ (150mg/m2 on days 10-14), and capecitabine (1500mg/m2 on days 10-14), and 177Lu-octreotate on day 10 each 8 weeks

19

Chi et al. 2022, China [36]

Randomized clinical trial

Patients with low or intermediate grade locally unresectable or metastatic pNET

TMZ (200mg on days 10-14), and tegafur (80-120mg on days 1-14) each 3 weeks

25

50 (45- 59.5)

63

7

16.2 (7.2- NE)

TMZ (200mg on days 10-14), tegafur (80-120mg on days 1-14), and thalidomide (100mg on days 1-7, 200mg on day 8-14 and 300mg from day 15) each 3 weeks

27

50.5 (43.5-57.2)

60

10

NE (7.1- EN)

Kunz et al. 2023, US [37]

Randomized clinical trial

Patients with low or intermediate grade locally unresectable or metastatic pNET

TMZ (200mg/m2 on days 1-5) each 4 weeks

65

Median: 60.3 (± 6 11.5)

54

Not reported

14.4

TMZ (200mg/m2 on days 1-5), and capecitabine (1500mg/m2 on days 10-14) each 4 weeks

68

Median: 61 (± 10.9)

56

22.7