Clinical Effect of Dose Escalation After Disease Progression in Patients With Metastatic Renal Cell Carcinoma.
Given the variability in drug levels with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC), dose escalation at the occurrence of progressive disease (PD) might have antitumor effects.



The data from patients with mRCC who were treated at the Cleveland Clinic with TKIs and received a dose escalation after PD in accordance with Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, were retrospectively reviewed. Patient- and disease-related data were collected and summarized as frequency counts and percentages or medians and ranges. The Kaplan-Meier method was used to summarize the treatment duration for the escalated doses.



Twenty-two patients were identified. Most patients (82%) were men; the median age at diagnosis was 58 years (range, 40-71 years). The most common histologic type was clear cell (73%). Axitinib was the most frequently escalated agent after PD (17 patients), followed by sunitinib (3 patients), and pazopanib (2 patients). Before PD, the median treatment duration was 6.8 months (range, 1.6-50.6 months). Of the 18 patients with evaluable tumor measurements after dose escalation, 14 (78%) had a decrease in tumor burden. The median decrease in tumor burden after dose escalation was 14% (range, 2%-58%); 4 patients (22%) had decreases ≥10%, 2 (11%) ≥20%, and 4 (22%) >30% (RECIST partial response). At the last follow-up examination, 5 patients (23%) continued to be treated at escalated doses. The median duration of escalated therapy was estimated at 10.1 months (range, 0.6 to 37.9 months).



Dose escalation of TKIs after PD for select patients with mRCC can lead to a reduction in tumor burden and extend the duration of therapy.
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. Electronic address: ornstem@ccf.org.
Moshe C
MC
Ornstein
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Laura
L
Wood
Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH.
Paul
P
Elson
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Kimberly
K
Allman
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Jennifer
J
Beach
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Allison
A
Martin
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Timothy
T
Gilligan
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Jorge A
JA
Garcia
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Brian I
BI
Rini
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D007191:Indazoles / Q000008:administration & dosage / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D000077210:Sunitinib; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden
D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C516667:pazopanib; D000077784:Axitinib; D000077210:Sunitinib
Dose titration; Progressive disease; RCC; Targeted therapy; Tyrosine kinase inhibitor