Introduction
Materials and methods
Eligibility criteria
[177Lu]Lu-DOTA-ZOL synthesis
Treatment protocol and follow-up
[177Lu]Lu-DOTA-ZOL infusion
Follow-up
Treatment response assessment
Primary outcome endpoint
Secondary outcome endpoints
Statistical analysis
Results
Patients
Variables | Number (%) |
---|---|
Age in years (mean ± SD, range) | 46.6 ± 15.08 (24–78) |
Gender | |
Male | 15 (37.5%) |
Female | 25 (62.5%) |
Primary disease | |
Prostate | 11 (27.5%) |
Breast | 23 (57.5%) |
Lung | 6 (15%) |
Baseline VAS pre-therapy (median, IQR) | 9 (8–10) |
Baseline KPS pre-therapy (median, IQR) | 60 (50–70) |
Baseline analgesic score (median) | 6 (6–8) |
The extent of skeletal metastases | |
< 6 | 2 (5%) |
6–20 | 17 (42.5%) |
> 20 | 7 (17.5%) |
Diffuse/superscan | 14 (35%) |
ECOG performance status | |
2 | 12 (30%) |
3 | 15 (37.5%) |
4 | 13 (32.5%) |
Mean cumulative activity (GBq) | 2.1 ± 0.6 GBq (1.3–2.7 GBq) |
Patient | Age/gender | Type of cancer | Previous therapy | Ongoing treatment | Analgesic score (type) | Analgesic score (quantity) |
---|---|---|---|---|---|---|
1 | 51/M | mCRPC | First- and second-generation anti-androgens, chemotherapy | Androgen synthesis inhibitor | Morphine | 2 |
2 | 25/F | Non-small cell right lung cancer | Lobectomy, chemotherapy, radiotherapy | – | Morphine | 2 |
3 | 60/M | Right breast cancer | Chemotherapy, radiotherapy | – | Morphine | 2 |
4 | 44/F | B/L breast cancer | B/L breast mastectomy, chemotherapy, radiotherapy, monoclonal antibody therapy | – | Morphine | 2 |
5 | 61/M | Right breast cancer | Hormonal therapy, chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 3 |
6 | 70/M | mCRPC | Medical castration, first-generation anti-androgen therapy, chemotherapy, radiotherapy | Second-generation anti-androgens | Morphine | 4 |
7 | 63/M | mCRPC | B/L orchidectomy, first-generation anti-androgens, chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
8 | 60/F | Small-cell lung cancer | Chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 3 |
9 | 44/F | Right breast cancer | Right breast mastectomy, hormonal therapy, chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
10 | 65/F | Left breast cancer | Hormonal therapy, chemotherapy, | – | Atypical opioids and non-morphine opioids | 2 |
11 | 33/F | Right breast cancer | Chemotherapy, radiotherapy | – | Morphine | 2 |
12 | 74/M | mCRPC | Radical Prostatectomy, B/L orchidectomy, first-generation anti-androgens, chemotherapy, | - | Atypical opioids and non-morphine opioids | 2 |
13 | 45/F | Left breast cancer | Left breast modified radical mastectomy, hormonal therapy, chemotherapy, radiotherapy, | – | Atypical opioids and non-morphine opioids | 3 |
14 | 27/F | B/L breast cancer | Hormonal therapy, B/L mastectomy, chemotherapy, radiotherapy, | – | Morphine | 2 |
15 | 47/F | Left breast cancer | Hormonal therapy, chemotherapy, radiotherapy, antibody therapy | – | Other NSAIDs | 1 |
16 | 27/F | Left breast cancer | chemotherapy, radiotherapy, | – | Other NSAIDs | 2 |
17 | 55/M | mCRPC | B/L orchidectomy, first- and second-generation anti-androgens, chemotherapy, radiotherapy | Androgen synthesis inhibitors | Other NSAIDs | 3 |
18 | 44/F | Left breast cancer | Left modified radical mastectomy, chemotherapy, radiotherapy | – | Morphine | 2 |
19 | 58/F | Right breast cancer | Rt breast mastectomy chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 4 |
20 | 24/M | Squamous cell cancer of lung | Surgery, chemotherapy | – | Morphine | 2 |
21 | 55/F | Left breast cancer | Surgery, chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
22 | 55/F | Squamous cell cancer of lung | Chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
23 | 54/F | Right breast cancer | Chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 3 |
24 | 40/F | Right breast cancer | Chemotherapy, radiotherapy | – | Morphine | 2 |
25 | 54/M | mCRPC | Medical castration, Chemotherapy, radiotherapy | Androgen-synthesis inhibitors | Morphine | 2 |
26 | 63/F | B/L breast cancer | Bilateral mastectomy, chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
27 | 47/F | Right breast cancer | Right breast mastectomy, hormonal therapy, chemotherapy, radiotherapy | – | Morphine | 2 |
28 | 50/M | Right breast cancer | Right modified radical mastectomy, chemotherapy, radiotherapy | – | Morphine | 2 |
29 | 40/F | B/L breast cancer | Hormonal therapy, chemotherapy, radiotherapy | – | Morphine | 2 |
30 | 75/M | mCRPC | B/L orchidectomy, chemotherapy, first- and second-generation anti-androgens, radiotherapy | None | Atypical opioids and non-morphine opioids | 2 |
31 | 67/M | mCRPC | B/L orchidectomy, first-generation anti-androgens Chemotherapy, radiotherapy, | Second-generation anti-androgens | Atypical opioids and non-morphine opioids | 2 |
32 | 78/M | mCRPC | B/L orchidectomy, chemotherapy | Androgen synthesis inhibitor | Atypical opioids and non-morphine opioids | 2 |
33 | 48/F | B/L breast cancer | Chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
34 | 40 | Right breast cancer | Right modified radical mastectomy, chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
35 | 70/M | mCRPC | Medical castration, chemotherapy, radiotherapy | Androgen-synthesis inhibitors | Morphine | 2 |
36 | 43/M | Non-small cell lung cancer of the right lung | Chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
37 | 32/F | Right breast cancer | Right breast mastectomy chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
38 | 67/F | Right breast cancer | Right modified radical mastectomy, hormonal therapy chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 2 |
39 | 30/F | Small cell cancer of lung | Chemotherapy, radiotherapy | – | Atypical opioids and non-morphine opioids | 3 |
40 | 76/M | mCRPC | B/L orchidectomy, first-generation anti-androgens, chemotherapy, radiotherapy | Second-generation anti-androgens | Atypical opioids and non-morphine opioids | 2 |
Treatment cycles and efficacy assessment
Extent of skeletal metastases | Number of patients (%) | Response according to VAS assessment criteria (number of patients) | Number of cycles administered | Response according to global pain assessment criteria (number of patients) | Number of cycles administered |
---|---|---|---|---|---|
< 6 | 2 (5%) | CR-1 | 2C | PR-2 | 1st patient-1C |
PR-1 | 1C | 2nd patient-2C | |||
6–20 | 17 (42.5%) | CR-5 | 4 patients-2C, 1 patient-1C | CR-1 | 2C |
PR-9 | 5 patients-2C, 4 patients-1C | PR-11 | 8 patients-2C, 3 patients-1C | ||
MR-1 | 2C | MR-3 | 2 patients-1C, 1 patient-2C | ||
NR-2 | Both patients-1C | NR-2 | Both patients-1C | ||
> 20 | 7 (17.5%) | CR-2 | 2 patients, 2C | CR-1 | 2C |
PR-4 | 3 patients-2C, 1 patient-1C | PR-4 | 3 patients-2C, 1 patient-1C | ||
MR-0 | 0 | MR-1 | 2C | ||
NR-1 | 1C | NR-1 | 1C | ||
Superscan/diffuse | 14 (35%) | CR-3 | All patients-2C | CR-0 | – |
PR-6 | 5 patients-2C, 1 patient-1C | PR-8 | 6 patients-2C, 2 patients-1C | ||
MR-4 | 1 patient-2C, 3 patients-1C | MR-5 | 3 patients-2C, 2 patients-1C | ||
NR-1 | 1 patient 1C | NR-1 | 1C |
Response (VAS criteria) | Number of patients (N) | Baseline AS (median, IQR) | Post-treatment AS (median, IQR) | P value |
---|---|---|---|---|
CR | 11 | 6 (6–8) | 2 (1.2–2.7) | 0.001 |
PR | 20 | 7 (6–8) | 3 (3–3.5) | < 0.0001 |
MR | 5 | 8 (6–8.25) | 4.8 (4–6) | 0.006 |
NR | 4 | 8.5 (8–12.5) | 8 (8–12) | 0.918 |
Response criteria | Breast cancer N = 23 | Prostate cancer N = 11 | Lung cancer N = 6 |
---|---|---|---|
CR | 9 | 2 | 0 |
PR | 11 | 7 | 2 |
MR | 3 | 0 | 2 |
NR | 0 | 2 | 2 |
Survival analysis
Toxicity
Parameters | Patients receiving single cycle | Patients receiving 2 cycles | ||||
---|---|---|---|---|---|---|
Baseline (median, IQR) | Post-treatment (median, IQR) | P value | Baseline (median, IQR) | Post-treatment (median, IQR) | P value | |
Haemoglobin (g/dL) | 10.2 (9.6–10.6) | 10 (8.9–11) | 0.129 | 14.7 (10–12.4) | 13 (9.2–11) | < 0.0001 |
Platelets (lakhs/µL) | 172 (140.2–198) | 143 (129.2–198.5) | 0.039 | 223 (164–284.25) | 217 (170–275.5) | 0.421 |
Leukocytes 109/L | 6760 (4210–11,800) | 5400 (3700–10,800 | 0.291 | 6700 (4280–12,000) | 5400 (3800–10,900) | 0.298 |
Creatinine (mg/dL) | 0.8 (0.63–0.96) | 0.79 (0.6–0.94) | 0.259 | 0.7 (0.7–0.9) | 0.8 (0.7–0.8) | 0.174 |
ALP (IU/L) | 282 (190–480) | 189 (140–280) | 0.0001 | 278 (186–390) | 230 (142–340) | 0.003 |