thus , taxane formulations with surfactants such as polysorbate 80 and ethanol have been approved for the management of several cancers , including prostate adenocarcinoma ( 14 ) .
however , ethanol and polysorbate 80 have the tendency to cause infusion - related toxicities and hypersensitivity reactions ( 57 ) . to avoid these adverse events , premedication with corticosteroids and antihistamines
furthermore , several new drug delivery systems have been researched , such as liposomes , polymeric micelles , protein and nanospheres ( 814 ) .
nanotechnology for drug delivery has achieved significant improvements in the efficacy and safety of drugs ( 1517 ) .
these nanoparticles are composed of organic substances , such as lipids , phospholipids , dextran and chitosan .
the drug particles are occasionally reduced in size to nanoparticles in order to avoid use of other substances as carriers ( 1820 ) .
we herein present the case of a patient with adenocarcinoma of the prostate with bone metastasis , who developed an allergic reaction to conventional docetaxel and was later started on doceaqualip , a nanosomal docetaxel lipid suspension ( ndls ) .
doceaqualip , which is devoid of polysorbate 80 and ethanol , was developed with lipids generally recognized as safe ( gras ) by the us food and drug administration .
doceaqualip has achieved a higher systemic availability of docetaxel when compared with conventional docetaxel in patients with solid tumors .
furthermore , the increased efficacy of doceaqualip compared with that of conventional docetaxel has been proven in patients with breast cancer without requirement for any premedication ( 18 ) .
a 65-year - old male patient from nairobi , kenya , initially presented with severe back pain in august , 2015 .
the patient was evaluated and diagnosed with adenocarcinoma of the prostate with bone metastasis after undergoing fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) .
prostate needle biopsy revealed adenocarcinoma of the prostate with a gleason score of 8 ( 4 + 4 ) and he was treated with goserelin acetate injection and bicalutamide tablets for ~3 months .
the patient had a history of hypertension that was controlled with treatment , and a history of transurethral resection of the prostate ( turp ) .
the patient had an eastern cooperative oncology group ( ecog ) performance status of < 2 .
a ga-68 prostate - specific membrane antigen ( psma ) pet / ct scan revealed post - turp changes , with small mild nodular hypermetabolism in the left posterior peripheral zone , likely representing residual prostatic disease .
1 ) , with a standardized uptake value ( suv ) of 10.5 for the prostate and 18.0 for skeletal lesions .
the serum prostate - specific antigen ( psa ) level was 0.32 ng / ml . the cardiac function was normal , with an ejection fraction of 62% .
chemohormonal therapy was planned and the patient was admitted for the first cycle of chemotherapy .
injection of docetaxel 120 mg , denosumab 120 mg and degarelix 240 mg was scheduled , with 5 cycles planned for docetaxel . following written informed consent ,
the first cycle was initiated with conventional docetaxel ( taxotere ) 120 mg after premedication with corticosteroids and antihistamines .
the patient developed an anaphylactic reaction ( bronchospasm , hypotension and skin rash ) within 5 min ; he was administered an iv injection of chlorpheniramine maleate ( avil ) , hydrocortisone and paracetamol , and recovered within 10 min .
after 12 h , the patient received 120 mg of the ndls doceaqualip , which was well - tolerated without any adverse reactions .
the patient subsequently received the next 3 cycles of chemotherapy with doceaqualip . a reassessment examination performed after the third cycle of chemotherapy with a ga-68 psma pet / ct scan ( fig .
1 ) showed mild interval regression of the small mild nodular hypermetabolism in the left posterior peripheral zone and morphologically stable heterogenous osteosclerotic lesions with internal regression of the metabolic activity .
no new metastases were observed , with an suv of 6.9 for the prostate and 19.4 for the skeletal lesions .
the patient received the fifth cycle of doceaqualip in march , 2016 , along with degarelix injection 80 mg , denosumab 120 mg , filgrastim 300 g and bicalutamide tablets 50 mg .
the patient was followed up 3 months later and the adenocarcinoma of the prostate had regressed considerably .
the taxanes paclitaxel ( taxol ) and docetaxel ( taxotere ) have been proven to be effective as first - line therapy for metastatic cancer in several randomized clinical trials and are widely prescribed chemotherapeutic agents ( 21,22 ) .
docetaxel is considered to be one of the more promising taxanes , and docetaxel formulations with polysorbate 80 and ethanol ( taxotere ) have been advocated in the management of different types of cancer , including prostate , non - small - cell lung , ovarian , breast and head and neck cancer .
polysorbate 80 in conventional docetaxel leaches plasticizers from polyvinylchloride infusion sets affecting the intravenously administered drug , and also causes hypersensitivity reactions , with the most common symptoms being bronchospasm , urticaria and hypotension ( 23 ) . to minimize these toxicities and avoid hypersensitivity reactions ,
however , corticosteroids are reported to cause hyperglycemia and increased infectious episodes ( 24 ) . fatalities due to polysorbate 80-containing docetaxel anaphylaxis may occur even after such prophylaxis ( 23 ) .
several formulations , such as taxane analogues and prodrugs , docetaxel - encapsulated nanoparticle - aptamer bioconjugates albumin nanoparticles , polyglutamates , emulsions , liposomes , docetaxel fibrinogen - coated olive oil droplets and submicronic dispersions , have been developed to avoid the abovementioned toxicities .
doceaqualip was primarily developed to avoid toxicities associated with polysorbate 80 and ethanol and to avoid premedication ( 18 ) .
doceaqualip is formulated with nano aqualip technology that has nano - carriers in suspension form , composed of gras lipids , and has demonstrated a better safety profile with a higher bioavailability compared with docetaxel ( 18 ) . moreover , even with premedication with corticosteroids and antihistamines , minor reactions ( e.g. , flushing and rash ) occur in ~40% of patients treated with conventional docetaxel ( 4,18,25 ) .
similarly , the patient described herein , who had adenocarcinoma of the prostate with extensive bone metastasis , developed an allergic reaction when administered conventional docetaxel with polysorbate 80 and ethanol , despite being premedicated with corticosteroids and antihistamines .
the patient was immediately administered iv corticosteroids and antihistamines to manage the allergic reaction , and the first cycle of ndls doceaqualip 120 mg ( 75 mg / m ) was later initiated , along with denosumab 120 mg and filgrastim 240 mg . the treatment was well - tolerated , without any adverse reactions .
the patient 's condition also improved , as evidenced with pet scans before and after the administration of doceaqualip ( fig .
the patient developed prostate cancer post - turp , which is consistent with the findings of karlsson et al ( 26 ) who suggested a mildly increased risk ( standardized incidence ratio : 1.26 ; 95% confidence interval : 1.171.35 ) of prostate cancer following turp ( 26 ) .
this case report further adds to the evidence that conventional docetaxel with polysorbate 80 and ethanol has the propensity to result in adverse reactions , despite premedication with corticosteroids and antihistamines .
the ndls doceaqualip may be an excellent tool in the management of prostate cancer with bone metastasis .
 docetaxel has been widely used in the treatment of several cancers , including adenocarcinoma of the prostate gland . 
 as docetaxel is insoluble in water , it must be administered with polysorbate 80 and ethanol , which are known to cause hypersensitivity reactions . 
 premedication with corticosteroids and antihistamines is advocated prior to docetaxel administration ; however , toxicities , occasionally fatal , have been reported , even with corticosteroid premedication . 
 we herein report the case of a patient with adenocarcinoma of the prostate , with bone metastasis and an eastern cooperative oncology group performance status of < 2 , who developed an allergic reaction to conventional docetaxel ( taxotere ) , despite being premedicated with corticosteroids and antihistamines . 
 the patient was managed with corticosteroids and antihistamines , and was later started on doceaqualip , a nanosomal docetaxel lipid suspension . 
 doceaqualip was well - tolerated by the patient and 5 cycles were subsequently administered , without any adverse reactions . 
 adenocarcinoma also regressed , as evidenced by positron emission tomography / computed tomography . 
Introduction
Case report
Discussion