Time for a Revision on the Role of PSA Response Rate as a Surrogate Marker for Median overall Survival in Docetaxel-based First-line Treatment for Patients with Metastatic hormone-refractory Prostate Cancer

e16151 Background: IV NVB plus hydrocortisone (HC) compared with HC alone resulted in improved clinical benefit, progression-free survival (PFS) and PSA response rate in HRPC. The oral formulation of NVB avoids the side effects associated with the IV injection, may reduce administration and toxicity-related costs and is easy to administer. Due to these advantages, single agent oral NVB treatment could be considered as an optimal option for patients (p) with HRPC previously treated with a taxane or as first-line treatment when a taxane is not indicated. We retrospectively evaluated efficacy and toxicity or oral NVB administered as single agent as first or second-line chemotherapy of metastatic HRPC. Methods: Retrospectively data was collected from p with metastatic HRPC treated with oral NVB 80 mg/m2 days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the first cycle, plus prednisone 10 mg/day. Patients had received a taxane as first-line treatment or had a documented contraindication to receiving docetaxel. 1 cycle was equivalent to a 3-week period. Results: Data on 55 p treated in 11 Spanish centres were included for assessment. Median age was 72.5 years (range 54–86). ECOG PS 0, 17%; 1, 66%; 2, 17%. Median PSA 75 ng/mL. Prior taxane chemotherapy, 87%. Median number of cycles was 4 (range 1–6). 53.8% of p could escalate oral NVB to 80 mg/m2. 221 cycles were performed, 4.1% were delayed and 3.2% had a dose reduction. Grade 3–4 events were infrequent and mainly haematological: neutropenia (5.5% of p), anemia (3.6%), pain (3.6%), infection (1.8%), asthenia (1.8%), respiratory (1.8%). No febrile neutropenia was reported. 49 p were evaluable for PSA response rate; complete plus partial response was observed in 20.4% (95% CI: 10.2% - 34.3%) and PSA stable was reported in 40.8%. 29 p were evaluable for measurable disease; among them, 20.7% presented partial response and 44.8% stable disease. Median follow-up was 4.3 months. Survival status: 49 p (89.1%) are alive and 6 p (10.9%) died. Conclusions: Oral NVB is a safe and active regimen in previous chemotherapy treated HRPC. For those p who can not receive a taxane as first-line therapy, oral NVB can also be considered as an effective first-line treatment. No significant financial relationships to disclose.

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Clinical experience with oral vinorelbine (NVBO) plus prednisone as first- or second-line chemotherapy of metastatic hormone-refractory prostate cancer (HRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15144 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15144-e15144

Author(s):

Jose Manuel Cervera Grau ◽

Miguel Beltran ◽

Iciar Garcia Carbonero ◽

Regina Girones ◽

Aranzazu Gonzalez del Alba ◽

...

Keyword(s):

Response Rate ◽

Single Agent ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Oral Vinorelbine ◽

Second Line Chemotherapy ◽

Psa Response ◽

Line Chemotherapy ◽

First Line Treatment

e15144 Background: IV NVB plus hydrocortisone (HC) compared with HC alone resulted in improved clinical benefit, progression-free survival (PFS) and PSA response rate in HRPC. The oral formulation of NVB avoids the side effects associated with the IV injection, may reduce administration and toxicity-related costs and is easy to administer. Due to these advantages, single agent NVBO treatment could be considered as an optimal option for patients (p) with HRPC previously treated with a taxane or as first-line treatment when a taxane is not indicated. We retrospectively evaluated efficacy and toxicity or NVBO administered as single agent as first or second-line chemotherapy of metastatic HRPC. Methods: Retrospectively data was collected from p with metastatic HRPC treated with NVBO 80 mg/m2 on days 1 and 8, with a prior test of myelosensitivity at 60 mg/m2 for the 1st cycle (cy), plus prednisone 10 mg/day. Patients had received either a taxane as 1st-line treatment or had a documented contraindication to receiving docetaxel. 1 cy was equivalent to a 3-week period. Results: Data on 67 p treated in 13 Spanish centres were included. Median age 73 years (range 54-86). ECOG PS 0, 16.4%; 1, 56.7%; 2, 11.9%. Median PSA 88.9 ng/mL. Prior chemotherapy, 58.2%. Median number of cy was 4 (range 1-6). 56.9% of p could escalate NVBO to 80 mg/m2. 265 cy were performed, 9.1% were delayed and 2.3% had a dose reduction. Grade 3-4 events were infrequent and mainly hematological: neutropenia (6% of p), anemia (4.5%), pain (3%), infection (1.5%), asthenia (3%), respiratory (1.5%), cystitis (1.5%), rectal bleeding (1.5%), febrile syndrome (1.5%), renal (1.5%). No febrile neutropenia was reported. PSA response rate 16.1%, PSA stable was reported in 41.9%. 39 p were evaluable for measurable disease; among them, PR 17.9%, SD 48.7%. Median follow-up, 7.1 months. Median overall survival, 11 months [95% CI: 7.3-14.7]. Median PFS, 2.9 months [95% CI: 2.2-3.6]. Conclusions: NVBO is a safe and active regimen in previous chemotherapy treated HRPC. For those p who cannot receive a taxane as first-line therapy, NVBO can also be considered as an effective first-line treatment.

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PSA response rate as a surrogate marker for median overall survival in docetaxel-based first-line treatments for patients with metastatic castration-resistant prostate cancer: an analysis of 22 trials

Tumor Biology ◽

10.1007/s13277-014-2559-8 ◽

2014 ◽

Vol 35 (11) ◽

pp. 10601-10607 ◽

Cited By ~ 15

Author(s):

Edoardo Francini ◽

Roberto Petrioli ◽

Giulia Rossi ◽

Letizia Laera ◽

Giandomenico Roviello

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Median Overall Survival ◽

Response Rate ◽

Surrogate Marker ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Castration Resistant ◽

Psa Response

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Vinorelbine plus prednisone versus docetaxel plus prednisone as first-line treatment in metastatic hormone-refractory prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15129 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15129-e15129 ◽

Cited By ~ 1

Author(s):

Inas Ibraheim Abdel Halim ◽

Wael M El Sadda ◽

Fatma Farouk ◽

Esam El Sherbeiny ◽

Mohamed S El Ashry

Keyword(s):

Prostate Cancer ◽

Therapeutic Option ◽

Similar Efficacy ◽

Therapeutic Benefit ◽

Phase Iii ◽

Hormone Refractory Prostate Cancer ◽

Line Treatment ◽

First Line ◽

Hormone Refractory ◽

First Line Treatment

e15129 Background: Metastatic hormone refractory prostate cancer (mHRPC) is not curable and all attempts at therapeutic intervention have been based on palliating the disease. Androgen dependent prostate carcinoma responds poorly to chemotherapy. Recent protocols using vinorelbine, mitoxantrone and docetaxel have significantly improved response rate, survival and pain control for those patients. The study aims to compare the therapeutic benefit of the use of vinorelbine versus docetaxel both plus prednisone in patients with mHRPC. Methods: Sixty pts (50% gpA, 50% gpB) were enrolled between Mar 2005 and Sep 2007. All patients had histologically confirmed prostatic adencarcinoma with evidence of metastatic disease and progression on hormonal therapy. WHO PS O-2, adequate marrow, liver and renal functions. Patients were randomized to gpA; Vinorellrine (V) IV 30mg/m2 d1 and 8, or gpB; Docetaxe (D) IV 75mg/m2 d1. All patients received 5mg of prednisone orally twice daily for 5 days starting on day 1 of the tudy. Cycles repeated every 3 weeks. Patients with PD went off the study while those with CR, PR or SD continued treatment for 8 cycles maximum. Results: All pts were evaluable for response, toxicity and survival. The median age (gpA, gpB): 59 and 58 years, median WHO PS 1 (range 0-2) in both groups , Median basal PSA were 110 (90-780) and 120 (80-850) in group A&B respectively. The overall response rates were 53.3% (gpA) and 56.7% (gpB) P=0.24, the rates of PSA decline were higher in gpA than gpB (80% vs 70%) (p=0.27). Reduction of pain was better in patients receiving (V) than those treated with (D) (60% vs 50%) (p= 0.23). The improvement in the quality of life was higher in gp A than in gpB (50% vs 40%) but the difference was statistically insignificant. No WHO G3 or 4 toxicities in gp A. G3 alopecia (60%), G3 neutropenia (20%) were noted in gpB. Conclusions: Our results suggest that vinorelbine and docetaxel demonstrate similar efficacy as first line treatment for mHRPC. Vinorelbine is however better tolerated besides being a less costly therapeutic option in Egypt. Comparative phase III trial is needed to confirm these results.

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Efficacy and tolerability of current treatments for hormone-refractory prostate cancer patients with visceral metastases

Future Oncology ◽

10.2217/fon-2020-1032 ◽

2021 ◽

Author(s):

Zeynep Oruç ◽

M. Ali Kaplan ◽

Mustafa Karaağaç ◽

Neslihan Özyurt ◽

Ali Murat Tatlı ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Treatment Options ◽

Hormone Refractory Prostate Cancer ◽

Line Treatment ◽

First Line ◽

Significant Difference ◽

Visceral Metastases ◽

Hormone Refractory ◽

First Line Treatment

Aim: To assess the efficacy and tolerability of the first-line treatment options for hormone-refractory prostate cancer patients with visceral metastases. Materials and methods: The records of 191 patients diagnosed with hormone-refractory prostate cancer with visceral metastases were analyzed retrospectively. Results: Docetaxel was administered to 61.2% (n = 117), abiraterone to 14.2% (n = 27) and enzalutamide to 9.4% (n = 18) as the first-line treatment. The median survival of the patients receiving docetaxel, abiraterone and enzalutamide as the first-line treatment during the hormone-refractory period was 15 (95% Cl: 12.9–17) months, 6 (95% Cl: 1.8–10.1) months and 11 (95% Cl: 0.9–23.1) months (p = 0.038), respectively. Conclusion: The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival.

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Weekly Docetaxel and Bortezomib as First-Line Treatment for Patients with Hormone-Refractory Prostate Cancer: A Minnie Pearl Cancer Research Network Phase II Trial

Clinical Genitourinary Cancer ◽

10.3816/cgc.2007.n.004 ◽

2007 ◽

Vol 5 (4) ◽

pp. 278-283 ◽

Cited By ~ 28

Author(s):

John D. Hainsworth ◽

Anthony A. Meluch ◽

David R. Spigel ◽

John Barton ◽

Lisa Simons ◽

...

Keyword(s):

Prostate Cancer ◽

Phase Ii Trial ◽

Research Network ◽

Hormone Refractory Prostate Cancer ◽

Line Treatment ◽

First Line ◽

Cancer Research Network ◽

Weekly Docetaxel ◽

Hormone Refractory ◽

First Line Treatment

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A REVIEW ON THE ROLE OF TYROSINE KINASE INHIBITORS AVAILABLE FOR THE MANAGEMENT OF CHRONIC MYELOID LEUKEMIA

Era s journal of medical research ◽

10.24041/ejmr2020.34 ◽

2020 ◽

Vol 7 (2) ◽

pp. 205-211

Author(s):

Kaynat Fatima ◽

Syed Tasleem Raza ◽

Ale Eba ◽

Sanchita Srivastava ◽

Farzana Mahdi

Keyword(s):

Chronic Myeloid Leukemia ◽

Tyrosine Kinase ◽

Protein Kinases ◽

Tyrosine Kinase Inhibitors ◽

Myeloid Leukemia ◽

Kinase Inhibitors ◽

Line Treatment ◽

First Line ◽

First Line Treatment

The function of protein kinases is to transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues. Many of these kinases are linked to the initiation and development of human cancer. The recent development of small molecule kinase inhibitors for the treatment of different types of cancer in clinical therapy has proven successful. Significantly, after the G-protein-coupled receptors, protein kinases are the second most active category of drug targets. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI), approved for chronic myeloid leukemia (CML) treatment. Imatinib induces appropriate responses in ~60% of patients; with ~20% discontinuing therapy due to sensitivity, and ~20% developing drug resistance. The introduction of newer TKIs such as, nilotinib, dasatinib, bosutinib, and ponatinib has provided patients with multiple options. Such agents are more active, have specific profiles of side effects and are more likely to reach the necessary milestones. First-line treatment decisions must be focused on CML risk, patient preferences and comorbidities. Given the excellent result, half of the patients eventually fail to seek first-line treatment (due to discomfort or resistance), with many of them needing a third or even further therapy lines. In the present review, we will address the role of tyrosine kinase inhibitors in therapy for chronic myeloid leukemia.

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