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Annals of Oncology : Official Journal... Jun 2016For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors... (Review)
Review
BACKGROUND
For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents.
OBJECTIVE
To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients.
METHODS
PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers.
RESULTS
A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied.
CONCLUSION
Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy.
Topics: Androgen Receptor Antagonists; Benzamides; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Docetaxel; Humans; Male; Nitriles; Phenylthiohydantoin; Platinum Compounds; Prostatic Neoplasms, Castration-Resistant; Radium; Taxoids; Treatment Outcome
PubMed: 27052650
DOI: 10.1093/annonc/mdw156 -
The Oncologist 2005The belief that hormone-refractory prostate cancer (HRPC) is a chemotherapy-resistant disease has been effectively refuted by the results of two recent randomized phase... (Review)
Review
The belief that hormone-refractory prostate cancer (HRPC) is a chemotherapy-resistant disease has been effectively refuted by the results of two recent randomized phase III trials. The TAX327 trial compared weekly docetaxel, every-3-weeks (Q3W) docetaxel, and Q3W mitoxantrone plus prednisone in 1,006 patients with HRPC, and results demonstrated that survival was significantly longer with a docetaxel-based regimen than with mitoxantrone. That trial demonstrated that only Q3W docetaxel was significantly superior to mitoxantrone with respect to overall survival. Quality of life was also superior in the docetaxel groups. In the Southwest Oncology Group (SWOG) 9916 trial, 674 men with progressive HRPC were randomized to 3-week cycles of docetaxel plus estramustine or mitoxantrone plus prednisone. Overall and disease-free survival times were significantly longer in the docetaxel arm. Collectively, the results of these trials demonstrate that survival can be significantly improved with chemotherapy in patients with HRPC to an extent that is comparable with the survival benefits seen in other cancers considered sensitive to chemotherapy such as breast cancer. Among various research tasks in HRPC is the definition of potential surrogate end points for survival, which will facilitate the conduct of pivotal trials. Prostate-specific antigen (PSA) response rate and changes in PSA constructs (i.e., PSA doubling time and PSA velocity) are promising potential surrogate end points for future trials and are being actively evaluated at the present time. Until there is clear demonstration of a surrogate role for these alternative end points, survival remains the appropriate end point for phase III trials in HRPC. There is a need for safe and effective second- and third-line regimens for patients progressing after docetaxel, and these patients should enter clinical trials designed for this population. Mitoxantrone, vinorelbine, the platinum analogue satraplatin, and epothilone are among compounds that require careful testing in this setting. The addition of targeted therapies, such as the endothelin receptor antagonist, atrasentan, and angiogenesis inhibitors, such as thalidomide and bevacizumab, to docetaxel-based therapy is being evaluated. High-dose calcitriol may also be an effective addition to docetaxel. The extensive effort devoted to the evaluation of chemotherapy and other systemic modalities of treatment of HRPC is likely to yield additional clinical benefit for patients, making HRPC a more manageable, less lethal, and less debilitating disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Treatment Outcome
PubMed: 16368869
DOI: 10.1634/theoncologist.10-90003-30 -
Journal of Veterinary Internal Medicine 2011Satraplatin is the 1st orally bioavailable platinum anticancer drug.
BACKGROUND
Satraplatin is the 1st orally bioavailable platinum anticancer drug.
OBJECTIVE
Our objectives were to evaluate efficacy in vitro against a canine cancer cell line, to determine the maximally tolerated dose (MTD) of satraplatin in tumor-bearing dogs, to identify the dose-limiting and other toxicities in dogs, and to record pharmacokinetics (PK).
ANIMALS
Dogs with macro- or microscopic malignant neoplasia.
METHODS
D17 canine osteosarcoma cells first were evaluated in a clonogenic survival assay. Then, dogs with a diagnosis of malignant neoplasia were prospectively entered in standard 3 + 3 cohorts. Additional patients were entered at the MTD to assess efficacy. Total and free platinum (by ultrafiltrate) concentrations were determined with inductively coupled plasma mass spectroscopy.
RESULTS
Satraplatin inhibited clonogenic survival in vitro at clinically relevant and achievable concentrations. Twenty-three dogs were treated, 14 with PK evaluation. The MTD was 35 mg/m(2)/d for 5 days, repeated every 3-4 weeks. Bioavailability was 41%. PK variables (mean ± SD) at the MTD included T(max) 1.8 (± 0.7) hours, C(max) 72 (± 26) ng/mL, area under concentration (AUC)(0-24 h) 316 (± 63) h × ng/mL, and MRT 7 (± 1.3) hours. Higher AUC after the 5th versus the 1st dose suggested drug accumulation. Interestingly, platelets consistently reached nadir sooner than did neutrophils (day 14 versus 19). Myelosuppression was dose-limiting and gastrointestinal toxicity was mild.
CONCLUSIONS AND CLINICAL IMPORTANCE
Satraplatin was well tolerated in tumor-bearing dogs, thus warranting further investigation in a phase II trial.
Topics: Administration, Oral; Animals; Antineoplastic Agents; Area Under Curve; Cell Line, Tumor; Dog Diseases; Dogs; Female; Male; Mass Spectrometry; Maximum Tolerated Dose; Neoplasms; Organoplatinum Compounds
PubMed: 21564292
DOI: 10.1111/j.1939-1676.2011.0727.x -
Clinical Genitourinary Cancer Sep 2013We assessed the effect of excision repair cross-complementing group 1 (ERCC1) and x-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcomes with...
BACKGROUND
We assessed the effect of excision repair cross-complementing group 1 (ERCC1) and x-ray cross-complementing group 1 (XRCC1) gene polymorphisms on treatment outcomes with satraplatin and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy.
PATIENTS AND METHODS
Twenty-four patients were enrolled in this single arm study. The primary objective was to determine if the presence of ERCC1 Asn118Asn (N118N, 500C>T, rs11615) and XRCC1 Arg399Gln (R399Q, 1301G>A, rs25487) genetic variants might be associated with an impact on progression-free survival (PFS); secondary objectives included overall response, survival, and toxicity.
RESULTS
After population stratification by race, white patients carrying heterozygous or variant genotypes at the ERCC1 C>T locus had a >3-fold longer median PFS (5.8 vs. 1.8 months; 2P = .18, adjusted) and 5-fold longer median overall survival (OS) (15.7 vs. 3.2 months; 2P = .010, adjusted) than did patients carrying only wild-type alleles. For the XRCC1 G>A variant, without regard to race, patients carrying the wild-type GG alleles had a longer PFS (9.3 months) than those carrying GA or AA alleles (2.7 months; 2P = .02). Similarly, those carrying GG alleles did not reach median OS, whereas those carrying GA or AA alleles had a median OS of 9.6 months (2P = .12, adjusted). Multivariable analysis by using Cox proportional hazards modeling demonstrated that only XRCC1 was associated with PFS.
CONCLUSIONS
To our knowledge, this is the first prospective study to date in patients with metastatic castration-resistant prostate cancer that describes predictive germline polymorphisms of ERCC1 and XRCC1 for assessing the clinical activity of satraplatin.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; DNA-Binding Proteins; Disease-Free Survival; Docetaxel; Drug Resistance, Neoplasm; Endonucleases; Genotype; Humans; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Polymorphism, Single Nucleotide; Prednisone; Prostatic Neoplasms, Castration-Resistant; Taxoids; Treatment Outcome; X-ray Repair Cross Complementing Protein 1
PubMed: 23684781
DOI: 10.1016/j.clgc.2013.04.007 -
Urologic Oncology Jan 2014Satraplatin is an oral platinum compound that has demonstrated efficacy and tolerability in prostate cancer. Preclinical synergy between bevacizumab and platinum has...
BACKGROUND
Satraplatin is an oral platinum compound that has demonstrated efficacy and tolerability in prostate cancer. Preclinical synergy between bevacizumab and platinum has been noted.
METHODS
Docetaxel-pretreated metastatic castrate-resistant prostate cancer patients with disease progression were eligible. Satraplatin 80 mg/m(2) orally on days 1 to 5, prednisone 5mg twice daily, and bevacizumab 10mg/kg on day 1, and 15 mg/kg on day 15 were administered in 35-day cycles.
RESULTS
Thirty one patients were enrolled. Grade 3 or 4 toxicities were pulmonary embolism in 2 patients and thrombocytopenia in 1 patient. 31% of the patients had a ≥ 30% decline in prostate-specific antigen. Median time to progression was 7.0 months (90% confidence interval [CI] 4.7-8.5mo) and median overall survival was 11.2 months (90% CI 9.1-16.4 mo). Polymorphism in the excision repair cross-complementation-1 (ERCC-1) gene was associated with time to progression (hazard ratio = 1.91). A circulating tumor cell count ≥ 5 was moderately prognostic of overall survival (hazard ratio = 1.49) as compared with CTC <5.
CONCLUSIONS
The combination was tolerable, and revealed promising efficacy in metastatic castrate-resistant prostate cancer. ERCC1 genotype maybe predictive of clinical benefit with platinum-based therapy in metastatic prostate cancer.
Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; DNA-Binding Proteins; Disease Progression; Endonucleases; Genotype; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplastic Cells, Circulating; Organoplatinum Compounds; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 23433892
DOI: 10.1016/j.urolonc.2012.11.017 -
Pharmaceuticals (Basel, Switzerland) Feb 2022sulfocalix[n]arenes are promising host molecules that can accommodate various chemotherapeutic drugs. Pt(IV)-based complexes, including satraplatin and asplatin, are...
sulfocalix[n]arenes are promising host molecules that can accommodate various chemotherapeutic drugs. Pt(IV)-based complexes, including satraplatin and asplatin, are promising alternatives that overcome the shortcomings of Pt(II) complexes. In this study, asplatin has been synthesized by fusing acetylsalicylic acid (aspirin) and cisplatin. Furthermore, it has been characterized using H NMR, mass spectrometry, elemental analysis, and UHPLC. A host-guest complex of asplatin and -sulfocalix[4]arene (PSC4) has been developed and characterized using UV, Job's plot analysis, HPLC, and density functional theory (DFT) calculations. The experimental and computational investigations propose that a 1:1 complex between asplatin and PSC4 is formed. The stability constant of the designed complex has been determined using Job's plot and UHPLC and computed to be 9.1 × 10 M and 8.7 × 10 M, which corresponds to a free energy of complexation of -6.8 kcal mol, while the calculated value for the inclusion free energy is -13.2 kcal mol. Both experimentally and theoretically estimated complexation free energy show that a stable host-guest complex can be formed in solution. The in vitro drug release study displayed the ability of the complex to release its cargo at a cancerous pH (pH of 5.5). Additionally, the asplatin/PSC4 complex is shown to be biocompatible when tested on human skin fibroblast noncancerous cells, demonstrating the highest in vitro cytotoxic activity against (MCF-7), cervical (HeLa), and lung cancer cells (A-549), with IC values of 0.75, 2.15, and 3.60 µg/mL, respectively. This is as compared to either cisplatin (IC of 5.47, 5.94 and 9.61 µg/mL, respectively) or asplatin (IC of 1.54, 5.05 and 3.91 µg/mL, respectively). On the other hand, the free asplatin exhibited higher cytotoxicity on cancerous cells and lower toxicity on noncancerous cells. The outcomes of the present joint theoretical and experimental investigation reinforce the interest in platinum-based anticancer therapeutics when they are protected from undesired interactions and suggest the use of the PSC4 macromolecule as a promising carrier for Pt(IV) anticancer drugs. The formed asplatin/PSC4 inclusion complex may represent an effective chemotherapeutic agent.
PubMed: 35215372
DOI: 10.3390/ph15020259 -
Cancer Control : Journal of the Moffitt... Jul 2006Docetaxel has recently been found to improve survival in patients with metastatic androgen-independent prostate cancer (AIPC). Chemotherapy as a first-line option leaves... (Review)
Review
BACKGROUND
Docetaxel has recently been found to improve survival in patients with metastatic androgen-independent prostate cancer (AIPC). Chemotherapy as a first-line option leaves room for improvement, while second-line options are multiple and somewhat controversial.
METHODS
Clinically relevant articles focusing on chemotherapy drugs for metastatic prostate cancer and their mechanism of action and efficacy were reviewed from January 2004 through April 2006.
RESULTS
Docetaxel is the standard of care for AIPC. However, for doublets with docetaxel or second-line chemotherapy, multiple studies have shown interesting and promising results with calcitriol, thalidomide, bevacizumab, satraplatin, vaccines, ixabepilone, and atrasentan.
CONCLUSIONS
Docetaxel should be considered for first-line treatment of metastatic AIPC. Due to its progression-free survival of only 6 months, more effective drugs and drug combinations need to be developed to treat patients with AIPC. Combination treatments with docetaxel and other new agents are promising, but adequately powered phase III trials need to be conducted with survival as the principal endpoint for these promising drug combinations.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Humans; Male; Prostatic Neoplasms
PubMed: 16885915
DOI: 10.1177/107327480601300306 -
Platinum anticancer drugs and photochemotherapeutic agents: recent advances and future developments.Science Progress 2014Platinum-based chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are widely applied for the treatment of various types of tumours. Over the last few... (Review)
Review
Platinum-based chemotherapeutic drugs such as cisplatin, carboplatin and oxaliplatin are widely applied for the treatment of various types of tumours. Over the last few decades, a large variety of Pt(II) and Pt(IV) complexes have been developed to improve the applicability in a wider spectrum of cancers, increase their therapeutic window and reduce the dose-limiting side effects. Photodynamic therapy (PDT), which is the administration of a photosensitiser followed by visible light activation, is a promising route to avoid damage to healthy cells and the surrounding tissue. Transition metal complexes as photochemotherapeutic agents are an attractive option for further development in the field of photoactivated chemotherapy (PACT). These complexes exhibit different numbers and types of excited states which are easily accessible upon light irradiation, subsequently giving rise to the formation of various photoproducts that can enable a distinct mode of action. Platinum-diazido complexes are promising candidates for PACT due to the low cytotoxicity when irradiated with visible light. This review summarises the mode of action of current platinum anticancer drugs with cisplatin as a lead example and the development of non-conventional Pt(II) complexes. Background information regarding PDT the photophysical and photochemical properties of metal complexes is provided, as well as notable examples of photoactivated metal complexes with biological activity. Particular emphasis is placed on recent developments on platinum photoactivated drugs.
Topics: Amantadine; Antineoplastic Agents; Cisplatin; Clinical Trials as Topic; Humans; Light; Neoplasms; Organoplatinum Compounds; Photochemotherapy; Photosensitizing Agents
PubMed: 24800467
DOI: 10.3184/003685014X13904811808460 -
The Oncologist Apr 2023In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer...
BACKGROUND
In the phase III SPARC trial, satraplatin, an oral platinum analogue, demonstrated anticancer activity in men with metastatic castration-resistant prostate cancer (mCRPC). Repeat biopsies are uncommon in mCRPC, limiting the feasibility of tissue-based biomarkers. This phase II study sought to evaluate the feasibility and utility of blood-based biomarkers to identify platinum-sensitive mCRPC.
METHODS
Patients with mCRPC who had progressed on docetaxel were enrolled at a single center from 2011 to 2013. Subjects received satraplatin 80 mg/m2 by mouth daily on days 1-5 and prednisone 5 mg PO twice daily, on a 35-day cycle. Serial peripheral blood samples were collected for biomarker assessment.
RESULTS
Thirteen docetaxel-refractory mCRPC patients were enrolled, with a median age of 69 years (range 54-77 years) and median PSA of 71.7 ng/mL (range 0.04-3057). Four of 13 patients (31%) responded to satraplatin (defined as a PSA decline of ≥30%). Responders demonstrated improved time to disease progression (206 vs. 35 days, HR 0.26, 95% CI, 0.02-0.24, P = .003). A 6-gene peripheral blood RNA signature and serum tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were assessed as biomarkers, but neither was significantly associated with response to satraplatin.
CONCLUSION
In this small series, one-third of mCRPC patients responded to platinum-based chemotherapy. Peripheral blood biomarker measurement is feasible in mCRPC, though the biomarkers we investigated were not associated with platinum response. Other biomarkers, such as DNA damage repair mutations, should be evaluated.
Topics: Male; Humans; Middle Aged; Aged; Docetaxel; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Tissue Inhibitor of Metalloproteinase-1; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome
PubMed: 36519763
DOI: 10.1093/oncolo/oyac224 -
Annals of Oncology : Official Journal... Sep 2001The discovery of cisplatin more than two decades ago was the most important therapeutic advance in the treatment of ovarian cancer. Today, cisplatin or carboplatin in... (Review)
Review
The discovery of cisplatin more than two decades ago was the most important therapeutic advance in the treatment of ovarian cancer. Today, cisplatin or carboplatin in combination with paclitaxel is the most commonly used first-line treatment for patients with advanced ovarian cancer. Although platinum drugs remain a critical component of chemotherapy in this type of cancer, cumulative toxicities can limit their use. These toxicities include nephrotoxicity, neurotoxicity and ototoxicity with cisplatin and myelosuppression with carboplatin. Although these adverse events can often be managed, the interventions themselves can complicate and add to the costs of treatment. Importantly, acquired resistance to traditional platinum drugs often develops in patients with ovarian cancer and can limit the usefulness of these drugs. Research into new platinum drugs has focused on identifying compounds with improved tolerability profiles and, importantly, those which can circumvent mechanisms of platinum resistance. New platinum drugs currently under development that are showing promise in ovarian cancer include oxaliplatin, nedaplatin, satraplatin, BBR3464 and ZD0473. If the encouraging in vitro activity shown by new compounds, such as ZD0473 and BBR3464, translates into efficacy in the clinic, they may offer an extended spectrum of activity which includes patients with ovarian cancer resistant to the classical platinum drugs.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials as Topic; Drug Resistance, Neoplasm; Female; Humans; Organoplatinum Compounds; Ovarian Neoplasms
PubMed: 11697824
DOI: 10.1023/a:1012259625746