1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Division of Hematology-Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
3Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
Copyright © 2021 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
This study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Institutional Review Board of Asan Medical Center (IRB No. 2021-0262). Informed consent from the patients was waived.
Author Contributions
Conceived and designed the analysis: Kim HD, Im HS, Lee JL.
Collected the data: Kim HD, Im HS, Lee JL.
Contributed data or analysis tools: Kim HD, Im HS, Kim JH, Jeong H, Yoon SK, Park I, Lee JL.
Performed the analysis: Kim HD, Kim JH, Jeong H, Yoon SK, Park I, Lee JL.
Wrote the paper: Kim HD, Lee JL.
Conflict of interest
Lee JL reports grants, personal fees and other from Pfizer Korea, grants, personal fees and other from Ipsen Korea, personal fees and other from Sanofi Aventis, personal fees from Novartis Korea, personal fees and other from Astellas Korea, grants, personal fees and other from BMS, grants, personal fees and other from MSD, other from Myovant Science, grants and other from Merck, grants and other from Esai, other from Amgen, grants from Roche, grants and personal fees from AstraZeneca, outside the submitted work. All remaining authors have declared no conflicts of interest.
Variable | Full cohort (n=89) | eGFR ≥ 30 mL/min (n=68) | eGFR < 30 mL/min (n=21) | p-value |
---|---|---|---|---|
Age (yr) | 73 (67–78) | 72.5 (67–78) | 75 (65–80) | 0.389 |
Male sex | 63 (70.8) | 46 (67.6) | 17 (81.0) | 0.369 |
Clinical setting | ||||
Initially metastatic | 34 (38.2) | 24 (35.3) | 10 (47.6) | 0.448 |
Recurrent | 55 (61.8) | 44 (64.7) | 11 (52.4) | |
ECOG PS | ||||
0 | 8 (9.0) | 7 (10.3) | 1 (4.8) | |
1 | 50 (56.2) | 39 (57.4) | 11 (52.4) | 0.570 |
2 | 31 (34.8) | 22 (32.4) | 9 (42.9) | |
Diabetes mellitus | 23 (25.8) | 14 (20.6) | 9 (42.9) | 0.080 |
Hypertension | 45 (50.6) | 31 (45.6) | 14 (66.7) | 0.150 |
Primary tumor site | ||||
Bladder | 44 (49.4) | 32 (47.1) | 12 (57.1) | 0.714 |
Renal pelvis | 24 (27.0) | 19 (27.9) | 5 (23.8) | |
Ureter | 21 (23.6) | 17 (25.0) | 4 (19.0) | |
Previous surgical resection | 60 (67.4)a) | 45 (66.2) | 15 (71.4) | 0.855 |
Previous chemotherapy | ||||
Adjuvant | 7 (7.9) | 7 (10.3) | 0 | 0.227 |
Neoadjuvant | 12 (13.5) | 10 (14.7) | 2 (9.5) | |
Lymph node metastasis | 52 (58.4) | 38 (55.9) | 14 (66.7) | 0.533 |
Visceral.metastasis | 48 (53.9) | 34 (50.0) | 14 (66.7) | 0.276 |
Lung metastasis | 31 (34.8) | 25 (36.8) | 6 (28.6) | 0.669 |
Liver metastasis | 14 (15.7) | 7 (10.3) | 7 (33.3) | 0.028 |
Bone metastasis | 18 (20.2) | 12 (17.6) | 6 (28.6) | 0.436 |
No. of metastatic sites | ||||
0 | 6 (6.7) | 5 (7.4) | 1 (4.8) | 0.510 |
1 | 46 (51.7) | 37 (54.4) | 9 (42.9) | |
≥ 2 | 37 (41.6) | 26 (38.2) | 11 (52.4) | |
Hemoglobin < 10 g/dL | 25 (28.1) | 17 (25.0) | 8 (38.1) | 0.374 |
Use of contrast-enhanced CT at baseline | 76 (85.4) | 63 (92.6) | 13 (61.9) | 0.002 |
Use of contrast-enhanced CT at response evaluationb) | 62 (81.6) | 53 (88.3) | 9 (56.2) | 0.010 |
Values are presented as median (interquartile range) or number (%). CT, computed tomography; eGFR, estimated glomerular filtration rate; ECOG, Eastern Cooperative Oncology Group; PS, performance status.
a) Five cases of palliative resection were included in patients with initially metastatic disease,
b) For 76 patients whose disease evaluation was feasible.
eGFR ≥ 30 mL/min | eGFR < 30 mL/min | p-value | |
---|---|---|---|
No. of GCb cycles | 6 (2–6) | 2 (1–4) | 0.002 |
RDI of gemcitabine (%)a) | 91.9 (75.0–100) | 75.0 (43.8–81.2) | 0.005 |
RDI of carboplatin (%)a) | 100 (100–100) | 94.4 (50.0–100) | 0.005 |
Reason for discontinuation | |||
Completion of treatment | 24 (35.3) | 2 (9.5) | 0.256 |
Surgery | 2 (2.9) | 0 | |
PD | 22 (32.4) | 8 (38.1) | |
Clinical deterioration | 2 (2.9) | 2 (9.5) | |
Intolerance or toxicity | 10 (14.7) | 5 (23.8) | |
Follow-up loss | 7 (10.3) | 3 (14.3) | |
Refusal | 1 (1.5) | 1 (4.8) |
eGFR ≥ 30 mL/min | eGFR < 30 mL/min | p-value | |
---|---|---|---|
RECIST response category | |||
Complete response | 2 (2.9) | 0 | 0.013 |
Partial response | 32 (47.1) | 2 (9.5) | |
Stable disease | 21 (30.9) | 9 (42.9) | |
Progressive disease | 5 (7.4) | 5 (23.8) | |
Not evaluable | 8 (11.8) | 5 (23.8) | |
Objective response ratea) | 32 (56.7) | 2 (12.5) | 0.004 |
Clinical characteristics of the study patients
Variable | Full cohort (n=89) | eGFR ≥ 30 mL/min (n=68) | eGFR < 30 mL/min (n=21) | p-value |
---|---|---|---|---|
Age (yr) | 73 (67–78) | 72.5 (67–78) | 75 (65–80) | 0.389 |
Male sex | 63 (70.8) | 46 (67.6) | 17 (81.0) | 0.369 |
Clinical setting | ||||
Initially metastatic | 34 (38.2) | 24 (35.3) | 10 (47.6) | 0.448 |
Recurrent | 55 (61.8) | 44 (64.7) | 11 (52.4) | |
ECOG PS | ||||
0 | 8 (9.0) | 7 (10.3) | 1 (4.8) | |
1 | 50 (56.2) | 39 (57.4) | 11 (52.4) | 0.570 |
2 | 31 (34.8) | 22 (32.4) | 9 (42.9) | |
Diabetes mellitus | 23 (25.8) | 14 (20.6) | 9 (42.9) | 0.080 |
Hypertension | 45 (50.6) | 31 (45.6) | 14 (66.7) | 0.150 |
Primary tumor site | ||||
Bladder | 44 (49.4) | 32 (47.1) | 12 (57.1) | 0.714 |
Renal pelvis | 24 (27.0) | 19 (27.9) | 5 (23.8) | |
Ureter | 21 (23.6) | 17 (25.0) | 4 (19.0) | |
Previous surgical resection | 60 (67.4) |
45 (66.2) | 15 (71.4) | 0.855 |
Previous chemotherapy | ||||
Adjuvant | 7 (7.9) | 7 (10.3) | 0 | 0.227 |
Neoadjuvant | 12 (13.5) | 10 (14.7) | 2 (9.5) | |
Lymph node metastasis | 52 (58.4) | 38 (55.9) | 14 (66.7) | 0.533 |
Visceral.metastasis | 48 (53.9) | 34 (50.0) | 14 (66.7) | 0.276 |
Lung metastasis | 31 (34.8) | 25 (36.8) | 6 (28.6) | 0.669 |
Liver metastasis | 14 (15.7) | 7 (10.3) | 7 (33.3) | 0.028 |
Bone metastasis | 18 (20.2) | 12 (17.6) | 6 (28.6) | 0.436 |
No. of metastatic sites | ||||
0 | 6 (6.7) | 5 (7.4) | 1 (4.8) | 0.510 |
1 | 46 (51.7) | 37 (54.4) | 9 (42.9) | |
≥ 2 | 37 (41.6) | 26 (38.2) | 11 (52.4) | |
Hemoglobin < 10 g/dL | 25 (28.1) | 17 (25.0) | 8 (38.1) | 0.374 |
Use of contrast-enhanced CT at baseline | 76 (85.4) | 63 (92.6) | 13 (61.9) | 0.002 |
Use of contrast-enhanced CT at response evaluation |
62 (81.6) | 53 (88.3) | 9 (56.2) | 0.010 |
Values are presented as median (interquartile range) or number (%). CT, computed tomography; eGFR, estimated glomerular filtration rate; ECOG, Eastern Cooperative Oncology Group; PS, performance status.
a)Five cases of palliative resection were included in patients with initially metastatic disease,
b)For 76 patients whose disease evaluation was feasible.
Treatment profiles of gemcitabine plus carboplatin cycle according to eGFR
eGFR ≥ 30 mL/min | eGFR < 30 mL/min | p-value | |
---|---|---|---|
No. of GCb cycles | 6 (2–6) | 2 (1–4) | 0.002 |
RDI of gemcitabine (%) |
91.9 (75.0–100) | 75.0 (43.8–81.2) | 0.005 |
RDI of carboplatin (%) |
100 (100–100) | 94.4 (50.0–100) | 0.005 |
Reason for discontinuation | |||
Completion of treatment | 24 (35.3) | 2 (9.5) | 0.256 |
Surgery | 2 (2.9) | 0 | |
PD | 22 (32.4) | 8 (38.1) | |
Clinical deterioration | 2 (2.9) | 2 (9.5) | |
Intolerance or toxicity | 10 (14.7) | 5 (23.8) | |
Follow-up loss | 7 (10.3) | 3 (14.3) | |
Refusal | 1 (1.5) | 1 (4.8) |
Values are presented as median (interquartile range) or number (%). eGFR, estimated glomerular filtration rate; GCb, gemcitabine plus carboplatin; PD, progressive disease; RDI, relative dose intensity.
a)RDI was calculated for the first two cycles (i.e., cycles 1 and 2).
Response to gemcitabine plus carboplatin therapy according to eGFR
eGFR ≥ 30 mL/min | eGFR < 30 mL/min | p-value | |
---|---|---|---|
RECIST response category | |||
Complete response | 2 (2.9) | 0 | 0.013 |
Partial response | 32 (47.1) | 2 (9.5) | |
Stable disease | 21 (30.9) | 9 (42.9) | |
Progressive disease | 5 (7.4) | 5 (23.8) | |
Not evaluable | 8 (11.8) | 5 (23.8) | |
Objective response rate |
32 (56.7) | 2 (12.5) | 0.004 |
Values are presented as number (%). eGFR, estimated glomerular filtration rate; RECIST, Response Evaluation Criteria In Solid Tumors.
a)Analysis was performed excluding those whose therapeutic response was not evaluable.
Values are presented as median (interquartile range) or number (%). CT, computed tomography; eGFR, estimated glomerular filtration rate; ECOG, Eastern Cooperative Oncology Group; PS, performance status. Five cases of palliative resection were included in patients with initially metastatic disease, For 76 patients whose disease evaluation was feasible.
Values are presented as median (interquartile range) or number (%). eGFR, estimated glomerular filtration rate; GCb, gemcitabine plus carboplatin; PD, progressive disease; RDI, relative dose intensity. RDI was calculated for the first two cycles (i.e., cycles 1 and 2).
Values are presented as number (%). eGFR, estimated glomerular filtration rate; RECIST, Response Evaluation Criteria In Solid Tumors. Analysis was performed excluding those whose therapeutic response was not evaluable.