Hydration Methods for Cisplatin Containing Chemotherapy: A Systematic Review.

INTRODUCTION: Cisplatin-induced nephrotoxicity (CIN) can be prevented by fluid hydration, electrolyte supplementation, or forced diuresis; however, the best way to prevent CIN is still unknown. The aim of this study was to provide objective evidence on the optimal design of hydration schemes to prevent CIN based on an update of the literature. METHODS: A Pubmed and Embase search were conducted in December 2021 and repeated in April 2022 and March 2023. Two independent reviewers screened the articles. The included articles were categorized and reviewed per category. RESULTS: Twenty-seven articles met the inclusion criteria. The included studies varied widely. Four out of seven studies investigating diuretics found a protective effect of adding mannitol to the hydration scheme. All six studies investigating duration and amount of volume of hydration found that a short-hydration scheme resulted in less CIN than a longer hydration scheme. Seven out of nine articles evaluating the role of electrolytes found that magnesium supplementation reduced the risk of nephrotoxicity. Three studies investigated the safety of oral hydration and concluded that nephrotoxicity did not occur more frequently after oral hydration. CONCLUSION: The hydration scheme of cisplatin should be short and consist of a relatively small amount of volume. The scheme should include mannitol and magnesium supplementation. Head-to-head studies are needed to investigate the safety of furosemide compared with mannitol and the dose of mannitol and magnesium.

Bone-Targeting Radiopharmaceuticals as Monotherapy or Combined With Chemotherapy in Patients With Castration-Resistant Prostate Cancer Metastatic to Bone.

In patients with metastatic castration-resistant prostate cancer, bone is the most common site for metastases. Because of their osteoblastic character, these lesions are very suitable for treatment with bone-seeking radiopharmaceuticals (RPs). Nowadays, radium-223-chloride is the only RP with a proven benefit in overall survival, whereas the ß-emitting RPs are used for pain palliation. In the past, many trials that investigated RPs alone, or in combination with chemotherapy have been performed. Because of different designs, characteristics of included patients, and chemotherapeutical and RP regimens, interpretation of the promising data and positioning of RPs in the treatment of metastatic prostate cancer has become difficult. In this review, we provide an overview of the existing data per RP with a focus on the different RPs in combination with chemotherapy. Furthermore, we aim to clarify the benefits on pain response and quality of life. Finally, we focus on the optimal timing and use of biomarkers in the treatment of patients with castration-resistant prostate cancer with RPs.

A randomised phase II trial of docetaxel versus docetaxel plus carboplatin in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial.

BACKGROUND: Docetaxel is standard first-line chemotherapy for patients with metastatic castration-resistant prostate carcinoma (mCRPC). Docetaxel re-challenge has never been tested in a prospective randomised controlled study. As some studies support the addition of carboplatin to docetaxel, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel re-treatment in docetaxel pre-treated mCRPC patients. METHODS: Patients with mCRPC with a progression-free interval of ≥3 months after initial docetaxel treatment were randomised between docetaxel 75 mg/m2 or docetaxel 60 mg/m2 plus carboplatin AUC4. The primary end-point was progression-free survival (PFS; PSA/RECIST). RESULTS: Owing to insufficient recruitment, the study was discontinued early after inclusion of 75 patients (targeted 150) PFS and overall survival (OS) were comparable between both groups (median PFS 12.7 months (95% CI 9.9-17.5 months) with docetaxel monotherapy and 11.7 months (95% CI 8.5-21.0 months) with combination therapy (p = 0.98); OS 18.5 months (95% CI 11.8-24.5 months) versus 18.9 months (95% CI 16.0-23.7 months) (p = 0.79). An interim analysis (SEQTEST) showed that the null hypothesis could already be excepted, and no significant difference between both study arms was expected if inclusion would be completed. The incidence of grade 3-4 infections and gastrointestinal side-effects was numerical higher in the carboplatin arm (p = 0.056). CONCLUSION: This early terminated study suggests no benefit from the addition of carboplatin to docetaxel re-treatment in patients with mCRPC, whereas the combination resulted in more toxicity. Re-treatment with docetaxel monotherapy appears to be feasible, save and effective for patients with mCRPC and an initial good response to docetaxel. TRIAL REGISTRATION: NTR3070.

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.

PURPOSE: In patients with metastatic castration-resistant prostate cancer (mCRPC), bone-seeking radiopharmaceuticals, such as Re-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 Re-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/m + 2 cycles of cabazitaxel 20 mg/m in level 1, and 6 cycles of cabazitaxel 25 mg/m in level 2) were combined with 2 cycles of Re-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 (Re-HEDP) (thrombopenia grade 3 delaying the next treatment cycle). The cohort was expanded to 6 patients, with no further DLTs. No DLT occurred 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 Re-HEDP is feasible and generally well tolerated with similar hematologic toxicity compared with cabazitaxel monotherapy.

Benefits of Using Stereotactic Body Radiotherapy in Patients With Metachronous Oligometastases of Hormone-Sensitive Prostate Cancer Detected by [18F]fluoromethylcholine PET/CT.

INTRODUCTION: For patients with oligometastatic recurrence of prostate cancer (PC), stereotactic body radiation therapy (SBRT) represents an attractive treatment option, as it is safe without major side effects. The aim of this study was to investigate the impact of SBRT in delaying the start of androgen deprivation therapy (ADT). PATIENTS AND METHODS: Forty-three patients treated with SBRT for oligometastatic recurrence (< 5 metastases) of hormone-sensitive PC, defined with [18F]fluoromethylcholine positron emission tomography/computed tomography were included. As a control group, 20 patients with oligometastatic disease not treated with SBRT were identified from another hospital. Data were collected retrospectively. RESULTS: A post-SBRT prostate-specific antigen (PSA) response was seen in 29 (67.4%) of 43 patients. Median ADT-free survival (ADT-FS) was 15.6 months (95% confidence interval [CI], 11.7-19.5) for the whole group, and 25.7 months (95% CI, 9.0-42.4) for patients with a PSA response. Seven patients were treated with a second course of SBRT because of oligometastatic disease recurrence; the ADT-FS in this group was 32.1 months (95% CI, 7.8-56.5). Compared with the control group, the ADT-FS from first diagnosis of metastasis was significantly longer, with 17.3 (95% CI, 13.7-20.9) months versus 4.19 months (95% CI, 0.0-9.0), P < .001. Also, time between diagnosis of the metastasis until progression of disease during ADT use (castration resistance) was longer for the SBRT-treated patients (mean 66.6, 95% CI, 53.5-79.8, vs. 36.41, 95% CI, 26.0-46.8 months, P = .020). There were no grade III or IV adverse events reported. CONCLUSION: SBRT can safely and effectively be used to postpone ADT in appropriately selected patients with oligometastatic recurrence of PC.