A phase 1 trial of cabazitaxel combined with 188Re-hydroxyethylidene diphosphonate in patients with metastatic castration-resistant prostate cancer who progressed on or after a docetaxel-containing treatment the ReCab trial

Joyce M. Van Dodewaard-De Jong, Esther W. Bouman-Wammes, Haiko J. Bloemendal, Henk M.W. Verheul, John M.H. De Klerk, Alfons J.M. Van Den Eertwegh

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Abstract

Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as 188Re- hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with 188Re- HEDP and cabazitaxel in mCRPC patients. Methods: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion. In both dose levels, cabazitaxel (4 cycles of cabazitaxel 25 mg/m2 + 2 cycles of cabazitaxel 20 mg/m2 in level 1, and 6 cycles of cabazitaxel 25 mg/m2 in level 2)were combined with 2 cycles of 188Re-HEDP 40 MBq/kg (1.1 mCi/kg) (after the second and fourth cabazitaxel cycles). Three patients were planned for each dose level, expanding to 6 patients in case of a dose-limiting toxicity (DLT). A DLT is defined as any grade 4 toxicity, or grade 3 toxicity delaying the next treatment cycle. Results: Twelve patients were included, of whom 3 had progressive disease before the third cycle of cabazitaxel. In total, 1 DLT occurred (dose level 1) after treatment cycle 6 (188Re-HEDP) (thrombopenia grade 3 delaying the next treatment cycle). The cohort was expanded to 6 patients, with no further DLTs. No DLToccurred in dose level 2. The most important adverse events were of hematologic origin, followed by mild fatigue and diarrhea. Conclusions: Combination therapy with cabazitaxel and 188Re-HEDP is feasible and generally well tolerated with similar hematologic toxicity compared with cabazitaxel monotherapy.

Original languageEnglish
Pages (from-to)415-420
Number of pages6
JournalClinical Nuclear Medicine
Volume42
Issue number6
DOIs
Publication statusPublished - 2017

Cite this

@article{9df211f184b94c9785fc988a5060bd0f,
title = "A phase 1 trial of cabazitaxel combined with 188Re-hydroxyethylidene diphosphonate in patients with metastatic castration-resistant prostate cancer who progressed on or after a docetaxel-containing treatment the ReCab trial",
abstract = "Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as 188Re- hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with 188Re- HEDP and cabazitaxel in mCRPC patients. Methods: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion. In both dose levels, cabazitaxel (4 cycles of cabazitaxel 25 mg/m2 + 2 cycles of cabazitaxel 20 mg/m2 in level 1, and 6 cycles of cabazitaxel 25 mg/m2 in level 2)were combined with 2 cycles of 188Re-HEDP 40 MBq/kg (1.1 mCi/kg) (after the second and fourth cabazitaxel cycles). Three patients were planned for each dose level, expanding to 6 patients in case of a dose-limiting toxicity (DLT). A DLT is defined as any grade 4 toxicity, or grade 3 toxicity delaying the next treatment cycle. Results: Twelve patients were included, of whom 3 had progressive disease before the third cycle of cabazitaxel. In total, 1 DLT occurred (dose level 1) after treatment cycle 6 (188Re-HEDP) (thrombopenia grade 3 delaying the next treatment cycle). The cohort was expanded to 6 patients, with no further DLTs. No DLToccurred in dose level 2. The most important adverse events were of hematologic origin, followed by mild fatigue and diarrhea. Conclusions: Combination therapy with cabazitaxel and 188Re-HEDP is feasible and generally well tolerated with similar hematologic toxicity compared with cabazitaxel monotherapy.",
keywords = "Re-HEDP, Cabazitaxel, Metastatic CRPC, Radiopharmaceutical",
author = "{Van Dodewaard-De Jong}, {Joyce M.} and Bouman-Wammes, {Esther W.} and Bloemendal, {Haiko J.} and Verheul, {Henk M.W.} and {De Klerk}, {John M.H.} and {Van Den Eertwegh}, {Alfons J.M.}",
year = "2017",
doi = "10.1097/RLU.0000000000001604",
language = "English",
volume = "42",
pages = "415--420",
journal = "Clinical Nuclear Medicine",
issn = "0363-9762",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - A phase 1 trial of cabazitaxel combined with 188Re-hydroxyethylidene diphosphonate in patients with metastatic castration-resistant prostate cancer who progressed on or after a docetaxel-containing treatment the ReCab trial

AU - Van Dodewaard-De Jong, Joyce M.

AU - Bouman-Wammes, Esther W.

AU - Bloemendal, Haiko J.

AU - Verheul, Henk M.W.

AU - De Klerk, John M.H.

AU - Van Den Eertwegh, Alfons J.M.

PY - 2017

Y1 - 2017

N2 - Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as 188Re- hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with 188Re- HEDP and cabazitaxel in mCRPC patients. Methods: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion. In both dose levels, cabazitaxel (4 cycles of cabazitaxel 25 mg/m2 + 2 cycles of cabazitaxel 20 mg/m2 in level 1, and 6 cycles of cabazitaxel 25 mg/m2 in level 2)were combined with 2 cycles of 188Re-HEDP 40 MBq/kg (1.1 mCi/kg) (after the second and fourth cabazitaxel cycles). Three patients were planned for each dose level, expanding to 6 patients in case of a dose-limiting toxicity (DLT). A DLT is defined as any grade 4 toxicity, or grade 3 toxicity delaying the next treatment cycle. Results: Twelve patients were included, of whom 3 had progressive disease before the third cycle of cabazitaxel. In total, 1 DLT occurred (dose level 1) after treatment cycle 6 (188Re-HEDP) (thrombopenia grade 3 delaying the next treatment cycle). The cohort was expanded to 6 patients, with no further DLTs. No DLToccurred in dose level 2. The most important adverse events were of hematologic origin, followed by mild fatigue and diarrhea. Conclusions: Combination therapy with cabazitaxel and 188Re-HEDP is feasible and generally well tolerated with similar hematologic toxicity compared with cabazitaxel monotherapy.

AB - Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as 188Re- hydroxyethylidene diphosphonate (HEDP), are effective for pain palliation and have a marked antitumor effect. Cabazitaxel is the standard second-line chemotherapy for mCRPC patients. We performed a phase 1 study investigating the safety and feasibility of the combined treatment with 188Re- HEDP and cabazitaxel in mCRPC patients. Methods: Patients with mCRPC and documented disease progression on or after docetaxel were eligible for inclusion. In both dose levels, cabazitaxel (4 cycles of cabazitaxel 25 mg/m2 + 2 cycles of cabazitaxel 20 mg/m2 in level 1, and 6 cycles of cabazitaxel 25 mg/m2 in level 2)were combined with 2 cycles of 188Re-HEDP 40 MBq/kg (1.1 mCi/kg) (after the second and fourth cabazitaxel cycles). Three patients were planned for each dose level, expanding to 6 patients in case of a dose-limiting toxicity (DLT). A DLT is defined as any grade 4 toxicity, or grade 3 toxicity delaying the next treatment cycle. Results: Twelve patients were included, of whom 3 had progressive disease before the third cycle of cabazitaxel. In total, 1 DLT occurred (dose level 1) after treatment cycle 6 (188Re-HEDP) (thrombopenia grade 3 delaying the next treatment cycle). The cohort was expanded to 6 patients, with no further DLTs. No DLToccurred in dose level 2. The most important adverse events were of hematologic origin, followed by mild fatigue and diarrhea. Conclusions: Combination therapy with cabazitaxel and 188Re-HEDP is feasible and generally well tolerated with similar hematologic toxicity compared with cabazitaxel monotherapy.

KW - Re-HEDP

KW - Cabazitaxel

KW - Metastatic CRPC

KW - Radiopharmaceutical

UR - http://www.scopus.com/inward/record.url?scp=85014543925&partnerID=8YFLogxK

U2 - 10.1097/RLU.0000000000001604

DO - 10.1097/RLU.0000000000001604

M3 - Article

VL - 42

SP - 415

EP - 420

JO - Clinical Nuclear Medicine

JF - Clinical Nuclear Medicine

SN - 0363-9762

IS - 6

ER -