Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial

Fléchon, Aude; Pouessel, Damien; Ferlay, Céline; Pérol, David; Beuzeboc, Philippe; Gravis, Gwénaëlle; Joly, Florence; Oudard, Stéphane; Deplanque, Gaël; Zanetta, Sylvie; Fargeot, P.; Priou, Frank; Droz, Jean‐Pierre; Culine, Stéphane

doi:10.1093/annonc/mdr004

Cited by 125 publications

(109 citation statements)

References 22 publications

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“…NE variation was different according to the markers, with a higher decrease rate for NSE than CgA. This treatment seemed to be more active on NSE than CgA; this was in accordance with the results reported by Fléchon et al [31 ]that showed an NSE decrease for 31% of cases and a CgA decrease for 7%. Moreover, docetaxel/prednisone and curcumin acted similarly on PSA and tumor response regardless of the NE features (elevated or not).…”

Section: Discussionsupporting

confidence: 90%

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study

Mahammedi¹,

Planchat²,

Pouget³

et al. 2016

Oncology

113

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Objectives: Favorable phase I results justified this pilot phase II study to assess the efficacy of docetaxel/curcumin in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC). Methods: Thirty patients with progressing CRPC and a rising prostate-specific antigen (PSA) received docetaxel/prednisone in standard conditions for 6 cycles in combination with per os curcumin, 6,000 mg/day (day -4 to day +2 of docetaxel). The co-primary endpoint was the overall response rate determined by PSA and target assessments. An ancillary study assessed the seric values of chromogranin A (CgA) and neuron-specific enolase (NSE). Results: Twenty-six patients received the scheduled treatment, 2 progressed and 2 died before the end of treatment. A PSA response was observed in 59% of patients (14% of PSA normalization) and achieved within the first three cycles for 88% of responders. Partial response was reached for 40% of evaluable patients. The regimen was well tolerated, and no adverse event was attributed to curcumin. Twenty patients were 100% curcumin compliant. The PSA level and objective response rate were not correlated with the serum values of CgA and NSE. Conclusion: This study produced additional data on curcumin as a treatment for cancer, with a high response rate, good tolerability and patient acceptability, justifying the interest to conduct a randomized trial.

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Section: Discussionsupporting

confidence: 90%

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study

Mahammedi¹,

Planchat²,

Pouget³

et al. 2016

Oncology

113

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“…Of 41 patients treated, 13 (33%) obtained a serum NE marker response (>50% decrease of neuron specific enolase or chromogranin A). This study demonstrates that the association of etoposide and either cisplatin or carboplatin is active in poorly differentiated NE cancers (4). Another study performed by Fjällskog et al (5) also demonstrates that the combination of cisplatin and etoposide can produce significant responses in patients with heavily pretreated and poorly differentiated/rapidly progressing NE tumors.…”

Section: Introductionsupporting

confidence: 59%

Rapid progression of mixed neuroendocrine carcinoma-acinar adenocarcinoma of the prostate: A case report

Wei

Zheng

et al. 2016

Oncology Letters

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Abstract. The current study presents the case of a 78-year-old male with mixed neuroendocrine (NE) carcinoma-acinar adenocarcinoma of the prostate. The patient received endocrine therapy (maximal androgen blockade) after the initial diagnosis resulting in a significant decrease in serum prostate-specific antigen (PSA) level. The patient underwent transurethral resection of the prostate after 6 months of androgen-deprivation therapy for extraordinarily salient difficulty in urination, and histopathology demonstrated mixed NE carcinoma-acinar adenocarcinoma once again. The NE prostate cancer progressed rapidly even though the serum PSA was controlled at a low level on account of the endocrine therapy. Previous treatment protocols were replaced by combined chemotherapy and endocrine therapy, and the patient responded well. The patient's serum PSA remained at a low level, however, urethral dilatation for acute urinary retention was required again 5 months later and the lower urinary tract symptoms became increasingly evident. The patient eventually died of cachexia.. These findings indicate that mixed NE carcinoma-acinar adenocarcinoma has a higher degree of malignancy and that endocrine therapy for prostate cancer has a propensity to facilitate progression of this tumor.

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“…In a subsequent report studying docetaxel plus carboplatin, the objective response rate was 25% in chemonaive patients who also received with estramustine, and 8% in patients progressing despite docetaxel. 17 Fléchon and colleagues 18 studied etoposide and carboplatin in a phase II trial enrolling men with visceral metastase and/or elevated neuroendocrine markers. Of the 56 patients, 37% had liver metastases and the objective response rate in patients with visceral metastases was 8.9%.…”

Section: Discussionmentioning

confidence: 99%

ECF chemotherapy for liver metastases due to castration-resistant prostate cancer

Gupta¹,

Potvin²,

Ernst³

et al. 2014

CUAJ

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Introduction: Most men with metastatic castration-resistant prostate cancer (CRPC) have biochemical response to docetaxel, but the objective response rate is low. Liver metastases are uncommon with CRPC and associated with shorter survival. More active treatment might benefit these patients. Epirubicin, cisplatin and flurouracil (ECF) is a standard regimen for gastric cancer and response in CRPC liver metastases has been reported. We reviewed our experience with ECF in CRPC with the primary objective of determining its anti-tumour activity in patients with liver metastatic CRPC. Methods: Men with CRPC treated with ECF were identified from electronic databases and data were extracted from medical records. Men with tumours showing neuroendocrine features were excluded. Results: In total, we identified 14 CRPC patients treated with ECF were identified, of which 8 had liver metastases. The median age was 56 (range: 42-76) and all had multiple poor prognostic features. A median of 6 cycles of ECF were administered (range: 1-10) and toxicities were similar to previous reports. Of the 8 patients with liver metastases, 5 had partial remission. Conclusions: ECF was highly active in this small selected group of younger men with liver metastases from CRPC and multiple poor prognostic features. Despite important limitations, this is the third report of high objective response rates with ECF in CRPC. Objective response rates are low with current monotherapies. A higher probability of ORR is preferred for critical organ disease, therefore the anti-tumour activity should encourage testing of ECF in comparison to the most active current therapies.

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Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial

Abstract: The benefit-risk ratio of this regimen seems unfavorable due to poor response and high toxicity.

Cited by 125 publications

References 22 publications

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study

Rapid progression of mixed neuroendocrine carcinoma-acinar adenocarcinoma of the prostate: A case report

ECF chemotherapy for liver metastases due to castration-resistant prostate cancer

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