Clinical UM Guideline
This document addresses docetaxel, a chemotherapeutic agent from the taxane group of drugs used for the treatment of various types of cancers including, but not limited to: cancers of the breast, prostate, stomach, head and neck, and non-small-cell lung cancer. It is used alone or with other agents and acts by disrupting or inhibiting the microtubular network in cells.
Note: For additional information, please refer to the following related document:
Docetaxel is considered medically necessary for the treatment of any of the following indications:
Not Medically Necessary:
Docetaxel is considered not medically necessary for all other indications.
The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
|J9171||Injection, docetaxel, 1 mg [Docefrez, Taxotere]|
|C00.0-C14.8||Malignant neoplasm of lip, oral cavity, and pharynx|
|C15.30-C16.9||Malignant neoplasm of esophagus, stomach|
|C30.0-C32.9||Malignant neoplasm of nasal cavities, ear, sinuses, larynx|
|C33-C34.92||Malignant neoplasm of trachea, bronchus and lung|
|C40.00-C41.9||Malignant neoplasm of bone and articular cartilage of limbs, other and unspecified sites|
|C44.02||Squamous cell carcinoma of skin of lip|
|C44.121-C44.129||Squamous cell carcinoma of skin of eyelid, including canthus|
|C44.221-C44.229||Squamous cell carcinoma of skin of ear and external auditory canal|
|C44.320-C44.329||Squamous cell carcinoma of skin of other and unspecified parts of face|
|C44.42||Squamous cell carcinoma of skin of scalp and neck|
|C48.0-C48.8||Malignant neoplasm of retroperitoneum and peritoneum|
|C49.0-C49.9||Malignant neoplasm of other connective and soft tissue|
|C50.011-C50.929||Malignant neoplasm of breast|
|C53.0||Malignant neoplasm of endocervix|
|C54.0-C55||Malignant neoplasm of corpus uteri, uterus part unspecified|
|C56.1-C57.9||Malignant neoplasm of ovary, other and unspecified female genital organs|
|C60.0-C60.9||Malignant neoplasm of penis|
|C61||Malignant neoplasm of prostate|
|C64.1-C66.9||Malignant neoplasm of kidney, renal pelvis, ureter|
|C67.0-C67.9||Malignant neoplasm of bladder|
|C68.0||Malignant neoplasm of urethra|
|C73||Malignant neoplasm of thyroid gland|
|C76.0||Malignant neoplasm of head, face and neck|
|C77.0||Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck|
|C78.00-C78.02||Secondary malignant neoplasm of lung|
|C79.81||Secondary malignant neoplasm of breast|
|C79.82||Secondary malignant neoplasm of genital organs|
|C79.89||Secondary malignant neoplasm of other specified sites [thyroid]|
|C80.0-C80.1||Malignant neoplasm without specification of site|
|D00.00-D00.2||Carcinoma in situ of lip, oral cavity, pharynx, esophagus, stomach|
|D02.0||Carcinoma in situ of larynx|
|D02.20-D02.22||Carcinoma in situ of bronchus and lung|
|D05.00-D05.92||Carcinoma in situ of breast|
|D07.39||Carcinoma in situ of other female genital organs|
|D09.0||Carcinoma in situ of bladder|
|D09.3||Carcinoma in situ of thyroid and other endocrine glands|
|Z85.01||Personal history of malignant neoplasm of esophagus|
|Z85.028||Personal history of other malignant neoplasm of stomach|
|Z85.118||Personal history of other malignant neoplasm of bronchus and lung|
|Z85.21-Z85.22||Personal history of malignant neoplasm of larynx, nasal cavities, middle ear, and accessory sinuses|
|Z85.3||Personal history of malignant neoplasm of breast|
|Z85.43||Personal history of malignant neoplasm of ovary|
|Z85.46||Personal history of malignant neoplasm of prostate|
|Z85.51||Personal history of malignant neoplasm of bladder|
|Z85.59||Personal history of malignant neoplasm of other urinary tract organ [urethra]|
|Z85.810-Z85.819||Personal history of malignant neoplasm of lip, oral cavity, and pharynx|
|Z85.830||Personal history of malignant neoplasm of bone|
|Z85.850||Personal history of malignant neoplasm of thyroid|
Multiple docetaxel products are currently marketed in the U.S. and include: generic docetaxel, Docefrez, Taxotere and Docetaxel Injection (non-alcohol formula).
Prescribing information (2014) for Docefrez states it is U.S. Food and Drug Administration (FDA) approved for the following uses:
Prescribing information (2015) for Taxotere states it is FDA approved for the following uses:
*HRPC is also known as castrate-resistant prostate cancer
Additionally, included in this document are non-FDA approved indications for docetaxel that are based on drug compendia recommendations (National Comprehensive Cancer Network® NCCN Drugs & Biologic Compendium™ , Truven Health Analytics Inc., DrugPoints® Compendium, and the American Hospital Formulary Service® ), NCCN Clinical Practice Guidelines in Oncology and published peer reviewed literature.
Bladder cancers are divided into several types and may respond differently to treatments. More than 90% of bladder cancers are transitional cell (urothelial) carcinoma.
Two phase II clinical trials evaluated the safety and efficacy of docetaxel for bladder cancer. McCaffrey and colleagues (1997) assessed docetaxel in 30 subjects with advanced bladder transitional-cell carcinoma (TCC) after previous failure to respond to a cisplatin based therapy. Four of 30 subjects demonstrated a partial response (PR), with durations of response ranging from 3 to 8 months. The estimated median survival duration for all subjects was 9 months. Therapy was well tolerated with the exception of myelosuppression. Pectasides and colleagues (2002) evaluated a combination of weekly docetaxel, gemcitabine and cisplatin for advanced bladder TCC in 35 subjects naïve to chemotherapy. Ten subjects achieved a complete response (CR) and 13 achieved a PR. Median survival time was 15.5 months. Treatment toxicity was moderate and there were no treatment-related deaths.
In a more recent phase II study, Boukovinas and colleagues (2012) assessed the safety and efficacy of docetaxel, gemcitabine and cisplatin for locally advanced or metastatic urothelial cancer in 60 subjects naïve to chemotherapy. Eight subjects achieved a CR and 16 a PR. The median overall survival (OS) was 21.4 months. Treatment toxicity consisted of grade 3 and 4 neutropenia in 27 subjects and grade 3 and 4 thrombocytopenia in 5 subjects. There were 3 cases of febrile neutropenia and no treatment-related deaths.
The NCCN Drugs and Biologics Compendium (2017) indicates that docetaxel may be used to treat recurrent or locally advanced or metastatic disease under certain circumstances (category 2A recommendations). The NCCN Bladder Cancer Guideline (V2.2017) includes the use of docetaxel or paclitaxel for subsequent systemic therapy for locally advanced or metastatic disease (category 2A recommendations).
Types of malignant bone tumors include osteosarcoma, chondrosarcoma and Ewing's sarcoma. Osteosarcoma (also called osteogenic sarcoma) begins in the bone cells and is the most common primary bone cancer. Chondrosarcoma is cancer of bone cartilage cells and is the second most common primary bone cancer. Ewing's sarcoma (also called Ewing's tumor) is the third most common primary bone cancer, and the second most common in children.
The efficacy of the combination of gemcitabine and docetaxel as a treatment for sarcomas has been demonstrated as effective in several retrospective case reviews (Navid, 2008; Song, 2014). Navid and colleagues (2008) reported an overall objective response rate of 29% and a median duration of response of 4.8 months (range, 1.6-13 months) for treatment of refractory bone sarcoma. Song and colleagues (2014) reported an objective response rate of 23.5% and a median duration of response of 11.2 months (range, 2.8-14.6 months) for treatment of recurrent or refractory osteosarcoma.
According to the NCCN Bone Cancer Guidelines (V2.2017) and NCCN Drugs and Biologics Compendium (2017) docetaxel may be used as second line therapy in combination with gemcitabine for relapsed/refractory metastatic Ewing sarcoma or osteosarcoma (category 2A recommendations).
Breast cancer is a malignant tumor originating from the cells of the breast. According to the American Cancer Society (ACS) (2017), it is the most common cancer among American women, except for skin cancers. Breast cancer most commonly occurs in women, but may also develop in men. Multiple large randomized trials have demonstrated the safety and efficacy of docetaxel as treatment for breast cancer.
Martin and colleagues (2005) compared docetaxel plus doxorubicin and cyclophosphamide (TAC) with fluorouracil plus doxorubicin and cyclophosphamide (FAC) as adjuvant chemotherapy for operable node-positive breast cancer. A total of 1491 women with axillary node-positive breast cancer were randomized in a multi-center trial to receive adjuvant chemotherapy consisting of six cycles of treatment with either TAC or FAC. The primary endpoint was disease-free survival (DFS). At a median follow-up of 55 months, the estimated rates of DFS at 5 years were 75% among the 745 women randomly assigned to receive TAC and 68% among the 746 randomly assigned to receive FAC, representing a 28% reduction in the risk of relapse in the TAC group. The estimated rates of OS at 5 years were 87% and 81%, respectively. Treatment with TAC resulted in a 30% reduction in the risk of death. The most common side effect was grade 3 or 4 neutropenia reported in 65.5% in the TAC group and 49.3% in the FAC group.
In a randomized prospective phase III clinical trial, Jones and colleagues (2009) compared four cycles of standard-dose doxorubicin/cyclophosphamide (AC) (60/600 mg/m2 ; n=510) with docetaxel/cyclophosphamide (TC) (75/600 mg/m2 ; n=506), administered by intravenous infusion every 3 weeks in women with operable stage I-III invasive breast cancer. At a median of 7 years follow-up, the differences in DFS between TC and AC were significant (81% TC versus 75% AC) as was OS (87% TC versus 82% AC). TC was found to be superior to standard AC and was also tolerated in both younger and older women.
The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study assessed the safety and efficacy of pertuzumab + trastuzumab + docetaxel, as compared with placebo + trastuzumab + docetaxel, as first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. A total of 808 participants with HER2-positive, metastatic breast cancer were enrolled into the study. Participants were eligible if they had not received prior chemotherapy for metastatic disease. One hormonal treatment prior to randomization was allowed. The median progression free survival (PFS) was 18.5 months for those randomized to the group treated with pertuzumab + trastuzumab + docetaxel compared to a median PFS of 12.4 months in the control group treated with placebo + trastuzumab + docetaxel. The median number of treatment cycles per participant was 15 (range 1-50) in the control group and 18 (range 1-56) in the pertuzumab cohort. For both groups, the median number of cycles with docetaxel was 8; (range 1-41) for the control group and (range 1-35) for the pertuzumab group (Baselga, 2012).
After an additional year of follow-up, a second interim analysis of the data from the CLEOPATRA trial was performed. Swain (2013) reported a significant survival benefit for those treated with pertuzumab + trastuzumab + docetaxel combination as compared to the placebo group. The median OS for the pertuzumab group was not reached (95% confidence interval [CI], 42.4 months to not estimable [NE]) compared to 37.6 months (95% CI, 34.3-NE) for the placebo cohort. The number of deaths in the placebo group compared to the pertuzumab group was statistically significant (154 of 406 [38%] vs. 113 of 402 [28%]; hazard ratio [HR] 0.66, 95% CI, 0.52-0.84; p=0.0008). The median PFS was 12.4 months (95% CI, 10.4-13.5) for the placebo group and 18.7 months (16.2-21.6) for the pertuzumab group (HR 0.69, 95% CI, 0.58-0.81).
Swain and colleagues (2015) performed a 50 month follow-up of the CLEOPATRA trial and reported a median OS of 56.5 months (95% confidence interval [CI], 49.3 to not reached) in the group receiving pertuzumab + trastuzumab + docetaxel combination, as compared to 40.8 months (95% CI, 35.8 to 48.3) in the placebo combination group, a difference of 15.7 months. The authors reported that median PFS improved by 6.3 months in the pertuzumab + trastuzumab + docetaxel combination group.
The American Society of Clinical Oncology (ASCO) Clinical Practice Guideline for systemic therapy for treatment of advanced HER2 positive breast cancer (Giordano, 2014) includes a strong recommendation: "Clinicians should recommend the combination of trastuzumab, pertuzumab, and a taxane for first-line treatment, unless the patient has a contraindication to taxanes."
According to NCCN Breast Cancer guidelines (V1.2017) docetaxel may be used for treatment of metastatic or recurrent breast cancer as a single agent or in combination with capecitabine. Additionally, the combination of pertuzumab, trastuzumab and docetaxel are referred to as first line agents for HER2 positive disease. Other agents listed for treatment of HER2 positive disease include the combination of docetaxel and trastuzumab. NCCN includes docetaxel and cyclophosphamide as a preferred regimen for HER2 negative disease. Docefrez is FDA approved for use as single agent for the treatment of locally advanced or metastatic BC after chemotherapy failure. Taxotere is FDA approved for use as a single agent to treat locally advanced or metastatic breast cancer after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node-positive breast cancer.
Esophageal and Esophagogastric Junction Cancers
Cancer of the esophagus starts in the inner layers of the cells and grows outwards. The two main types of esophageal cancer are adenocarcinoma and squamous cell carcinoma.
Li and colleagues (2010) evaluated docetaxel-based concomitant chemoradiotherapy for the treatment of esophageal squamous cell carcinoma to determine clinical response and OS. The single center trial consisted of 59 individuals with squamous cell carcinoma of the esophagus staged II to IV. Radiotherapy was delivered and two cycles of a regimen containing docetaxel (60 mg/m2 ) and cisplatin (80 mg/m2 ) were given every 3 weeks during the period of radiotherapy. The overall response rate was 98.3%, with 42 complete responses and 26 partial responses. During the follow-up time (median 18 months, 4 to 53 months), the median OS time was 22.6 months. The rate of locoregional progression-free survival, progression-free survival, and OS in 3 years was 59.6%, 29.2%, and 36.7%, respectively. Hematologic toxicity grade 3 and grade 4 were observed in 39.0% and 20.3% of cases respectively, with severe non-hematologic acute toxicity being infrequent. The authors reported that definitive concomitant chemoradiotherapy with docetaxel and cisplatin in squamous cell esophageal carcinoma was associated with a satisfactory outcomes and manageable toxicity.
The NCCN Esophageal and Esophagogastric Junction Cancer Guidelines (V1.2017) and NCCN Drugs and Biologics Compendium (2017) include category 1 and 2A recommendations for the use of docetaxel to treat esophageal and esophagogastric junction cancers.
The majority of gastric or stomach cancers are adenocarcinomas. Gastric adenocarcinoma originates from the inner most lining of the stomach.
Van Cutsem and colleagues (2006) randomly assigned 445 individuals with advanced gastric cancer to either docetaxel 75 mg/m2 and cisplatin 75 mg/m2 (day 1) plus fluorouracil 750 mg/m2 (days 1 to 5) (DCF) every 3 weeks or cisplatin 100 mg/m2 (day 1) plus fluorouracil 1,000 mg/m2 (days 1 to 5) (CF) every 4 weeks. The primary endpoint was time to progression (TTP). TTP was longer with DCF versus CF (32% risk reduction). OS was longer with DCF versus CF (23% risk reduction; log-rank p=0.02). Two year survival rate was 18% with DCF and 9% with CF. Overall response rate was higher with DCF. Grade 3 to 4 treatment-related adverse events occurred in 69% (DCF) versus 59% (CF) of cases.
The NCCN Gastric Cancer Guidelines (V1.2017) and NCCN Drugs and Biologics Compendium (2017) include category 1 and 2A recommendations for the use of docetaxel to treat gastric cancers. Additionally, Taxotere is FDA approved for the treatment of GC: with cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction.
Head and Neck Cancer
Head and neck cancers usually begin in the squamous cells that line moist, mucosal surfaces inside the head and neck (for example, inside the mouth, nose and throat). They are typically referred to as squamous cell carcinomas of the head and neck. Head and neck cancers can also begin in the salivary glands, but these are much less common.
Two randomized trials (Posner, 2007; Vermorken, 2007) demonstrated the efficacy of docetaxel for head and neck cancer. A total of 859 individuals from both trials received induction chemotherapy with cisplatin and fluorouracil, with or without docetaxel, followed by radiotherapy or chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck. Those receiving docetaxel/cisplatin/fluorouracil had prolonged OS (71 versus 30 months) as compared to those receiving cisplatin/fluorouracil as induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck.
The NCCN Head and Neck Cancers Guideline (V1.2017) and NCCN Drugs and Biologics Compendium (2017) include category 1 and 2A recommendations for the use of docetaxel to treat head and neck cancers. Additionally, Taxotere is FDA approved the treatment of squamous cell carcinoma of head and neck cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN.
The most common form (85%) of lung cancer is non-small cell lung cancer. Subtypes of non-small cell lung cancer are squamous cell carcinoma, adenocarcinoma and large cell carcinoma. Small cell lung cancer (also called oat cell cancer) and lung carcinoid tumors are less common forms of lung cancer. Small cell lung cancers typically spread quickly and lung carcinoid tumors are slow growing and rarely spread.
Fossella and colleagues (2003) conducted a randomized phase III study of 1218 individuals with unresectable stage IIIB or stage IV non-small cell lung cancer treated with docetaxel and cisplatin (DC), vinorelbine and cisplatin (VC), or docetaxel and carboplatin (DCb). Persons treated with DC had a median survival of 11.3 versus 10.1 months for those treated with VC. The 2 year survival rate was 21% for the DC group and 14% for those treated with VC. Median survival was similar in those receiving DC compared to those receiving VC.
Additionally, several phase II studies have demonstrated promising results for the treatment of small cell lung cancer with treatment regimens containing docetaxel (Smythe, 1994; Takiguchi, 2014).
The NCCN Non-Small Cell Lung Cancer Guideline (V5.2017) and NCCN Drugs and Biologics Compendium (2017) include category 1 and 2A recommendations for the use of docetaxel to treat non-small lung cancer. Additionally, the NCCN Small Cell Lung Cancer Guideline (V3.2017) and NCCN Drugs and Biologics Compendium (2017) include a category 2A recommendation for the use of docetaxel as subsequent systemic therapy to treat small lung cancer. Docefrez and Taxotere are FDA approved as single agents for locally advanced or metastatic non-small cell lung cancer after platinum therapy failure; and with cisplatin for unresectable, locally advanced or metastatic untreated non-small cell lung cancer.
Occult Primary Tumors
Occult primary tumors or cancer of unknown primary site (CUP) are a group of heterogeneous tumors that have clinical characteristics of metastatic disease with no known origin at the time of therapy.
In 2004, Pouessel and colleagues reported that a combination of gemcitabine and docetaxel was active and well tolerated as first-line therapy for occult primary tumors. Thirty-five individuals were assessed for response and survival. One complete and 13 PRs were achieved. The overall response rate was 40% and the median time to disease progression was 2 months. The median OS time was 10 months (range, 0-32 months). Toxicity was reported as manageable.
Demirci and colleagues (2014) retrospectively evaluated a multi-center experience of docetaxel and cisplatin combination therapy for CUP. A total of 29 cases of pathologically confirmed subtypes of CUP were included in the study. The combination of docetaxel (75 mg/m2 , day 1) and cisplatin (75 mg/m2 , day 1) was administered as a first line regimen every 21 days for a median of 3 cycles. Multimetastatic disease was confirmed at time of initial diagnosis in 17 cases. Histopathological diagnoses were well-moderate differentiated adenocarcinoma (51.7%), undifferentiated carcinoma (27.6%), squamous cell cancer (13.8%), mucoepidermoid carcinoma (3.4%) and neuroendocrine differentiated carcinoma (3.4%). Objective response rate was 37.9% and clinical benefit was 58.6%. Median PFS and OS were 6 months (range, 4.3-7.7 months) and 16 months (range, 8.1-30.9 months), respectively. Fourteen cases (60.8%) were treated in a second line setting. There were no treatment related deaths. Most common toxicities were nausea-vomiting (44.6%) and fatigue (34.7%).
The NCCN Occult Primary Guideline (V2.2017) and NCCN Drugs and Biologics Compendium (2017) include category 2A recommendations for the use of docetaxel to treat occult primary adenocarcinoma or squamous cell carcinoma.
The ovaries are made up of three main kinds of cells that develop into different tumor types. The majority of ovarian tumors are epithelial cell tumors originating from outer surface cells. Other types of ovarian tumors are germ cell tumors that originate from the ova and stromal tumors that originate from ovarian structural tissue cells. Fallopian tube and primary peritoneal cancers are rare forms and are similar to epithelial cell tumors.
Phase II and phase III clinical trials have demonstrated the safety and efficacy of docetaxel used for treatment of ovarian cancer, including fallopian tube and primary peritoneal cancer. Rose and colleagues (2003) performed a phase II study of docetaxel in paclitaxel-resistant ovarian and peritoneal carcinoma. A total of 60 women with platinum- and paclitaxel-resistant ovarian or peritoneal cancer were treated with docetaxel 100 mg/m2 intravenously every 21 days. Responses were observed in 22.4% of subjects. A CR occurred in 5.2% and a PR occurred in17.2% (95% CI, 12.5-35.3%). The median duration of response was 2.5 months. The primary adverse effect was grade 4 neutropenia. Dose reductions were required in 36% due to adverse effects. The authors concluded that docetaxel was active in paclitaxel-resistant ovarian and peritoneal cancer; however, further study was recommended to determine optimal scheduling and dosage.
A large randomized phase III trial (Vasey, 2004) compared the combination of docetaxel and carboplatin to paclitaxel and carboplatin as first-line chemotherapy for stage Ic–IV epithelial ovarian or primary peritoneal cancer. A total of 1077 women were randomized to receive docetaxel at 75 mg/m2 or paclitaxel at 175 mg/m2 . Both treatments were followed by carboplatin and repeated every 3 weeks for 6 cycles. After a median follow-up of 23 months, both groups had similar PFS (medians of 15.0 months for docetaxel-carboplatin and 14.8 months for paclitaxel-carboplatin) and OS at 2 years (64.2% and 68.9%, respectively). Additionally, the combination of docetaxel-carboplatin was associated with substantially less overall and grade 2 or higher neurotoxicity than paclitaxel-carboplatin.
Straus and colleagues (2007) studied docetaxel and carboplatin for the treatment of relapsed ovarian, peritoneal and tubal cancer. A total of 25 women (age 18-75 years) were enrolled in this phase II clinical trial. Docetaxel 75 mg/m2 was given on day 1 followed by carboplatin on day 1. In the intent-to-treat population, there were 16 (64.0%) CR and 2 (8.0%) PRs, resulting in an overall response rate of 72.0%. Three women (12.0%) achieved stable disease and 2 others (8.0%) had disease progression. The authors reported that the combination of docetaxel and carboplatin was highly active and well tolerated in women with recurrent platinum-sensitive ovarian, peritoneal and tubal cancer.
The NCCN Ovarian Cancer (including Fallopian Tube Cancer and Primary Peritoneal Cancer) Guideline (V1.2016) and NCCN Drugs and Biologics Compendium (2017) include category 1 and 2A recommendations for the use of docetaxel as treatment for ovarian cancer including fallopian tube and primary peritoneal cancer.
Penile cancer is rare in developed countries and clinical trial data are limited due to this rarity. According to the American Cancer Society (ACS) (2017) penile diagnosed in less than 1 man in 100,000 each year and accounts for less than 1% of cancers in men in the United States.
Two small recent studies have evaluated a docetaxel containing regimen for the treatment of penile cancer. Djajadiningrat and colleagues (2015) assessed the objective response of penile cancer neoadjuvantly treated with taxane-based combination chemotherapy. Secondary outcomes were PFS, disease-specific survival (DSS), and toxicity. A total of 26 men were treated in a nonrandomized study with 4 courses of docetaxel, cisplatin, and 5-fluorouracil for advanced penile cancer between 2008 and 2012. At a median follow-up of 30 months, an imaging-based response was obtained in 60%. A pathologic complete response was observed in 1 of 25 evaluable men (4%; 95% CI, 0%-20%). Toxicity was considerable and registered in every subject. The 2 year PFS and DSS probability were 12% and 28%, respectively. Subjects responsive to chemotherapy had significantly better survival than nonresponsive subjects.
Zhang and colleagues (2015) conducted a single institution open-label phase II study evaluating docetaxel, cisplatin, and fluorouracil for treatment of distantly metastatic penile cancer. A total of 39 chemotherapy naïve men with histologically confirmed, distantly metastatic, measurable penile squamous carcinomas were enrolled between November 2009 and July 2013. All subjects were treated with docetaxel 75 mg/m2 (day1), cisplatin 70 mg/m2 (day1), and fluorouracil 500 mg/ m2 /d (days 1 to 5) every 3 weeks as first line chemotherapy. The primary endpoint was objective response rate (ORR). The median follow-up time was 11 months. A total of 15 men had a confirmed objective response, all of which were partial responses. The median PFS was 3 months and the median OS was 7 months. The most frequent adverse events of grade 3 or higher were neutropenia (13 of 39; 33%), nausea/vomiting (7 of 39;18%). No treatment-related deaths occurred.
Historic NCCN Penile Cancer Guidelines (V1.2014) stated "palliative options may include docetaxel as a single agent." Current NCCN Penile Cancer Guidelines (V2.2017) report that no standard subsequent-line systemic therapy exists. NCCN recommends consideration of participation in a clinical trial as data are limited for second-line therapy. However, specialty consensus opinion suggests that docetaxel may be considered as a treatment option for penile cancer.
According to the American Cancer Society (ACS) (2017), prostate cancer is the most common form of cancer, other than skin cancer, among men in the United States. Large randomized clinical trials have demonstrated the efficacy of docetaxel for the treatment of prostate cancer.
Tannock and colleagues (2004) conducted a randomized, nonblinded, phase III multi-center study (TAX 327) that evaluated docetaxel plus prednisone or mitoxantrone plus prednisone for treatment of advanced prostate cancer. A total of 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were also randomized to receive mitoxantrone, or docetaxel administered every 3 weeks, or weekly docetaxel. The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the docetaxel every 3 weeks group, and 17.4 months in the weekly docetaxel group. Adverse events were more common those treated with docetaxel.
Berthold and colleagues (2008) performed a follow-up of the TAX 327 study. Investigators were asked to provide the date of death or last follow-up of all participants who remained alive in August 2003. The original analysis took place in August 2004 at which time 557 deaths had occurred. By March 2007, there were 310 additional deaths resulting in a total of 867. The survival benefits of docetaxel given every 3 weeks compared with mitoxantrone persisted in the extended follow-up. Median survival time was 19.2 months in the docetaxel every 3 weeks arm, 17.8 months in the docetaxel weekly arm and 16.3 months in the mitoxantrone arm. The authors concluded "docetaxel administered every 3 weeks with prednisone remains the preferred treatment option for most patients with metastatic hormone resistant prostate cancer."
The NCCN Prostate Cancer Guideline (V2.2017) and NCCN Drugs and Biologics Compendium (2017) include category 1 and 2A recommendations for the use of docetaxel as treatment for prostate cancer. Docefrez and Taxotere are FDA approved for use with prednisone for the treatment of androgen independent (hormone refractory) metastatic prostate cancer.
Soft Tissue Sarcoma
Soft tissue sarcomas are uncommon and develop from soft tissues such as fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.
In a randomized phase II trial (Maki, 2007) compared the combination of docetaxel and gemcitabine to gemcitabine alone for the treatment of metastatic soft tissue carcinomas. A total of 119 of 122 subjects had assessable outcomes. Median PFS was 6.2 months for gemcitabine-docetaxel and 3.0 months for gemcitabine alone. Median OS was 17.9 months for gemcitabine-docetaxel and 11.5 months for gemcitabine. The authors concluded that docetaxel and gemcitabine resulted in superior PFS but with increased toxicity.
The NCCN Soft Tissue Sarcoma Guideline (V2.2017) and NCCN Drugs and Biologics Compendium (2017) include category 2A recommendations for the use of docetaxel as a treatment of soft tissue sarcomas.
Thyroid Carcinoma (Anaplastic)
Anaplastic thyroid carcinoma (ATC) is the most uncommon form of thyroid cancer. It is a very aggressive disease with an extremely poor prognosis and occurs most often in the elderly. Clinical trial data are limited due to the rarity of the disease; however, there are encouraging reports of docetaxel being used for the treatment of ATC. In 2010, Troch and colleagues performed a retrospective analysis of six cases of ATC treated at a single institution. A total of four complete responses and two partial responses were reported with the combined use of docetaxel and radiation therapy. Five of six individuals survived after a median follow up of 21.5 months (range, 2–40 months). Foote and colleagues (2011) reported on 10 consecutive cases of regionally confined ATC treated with a combination of radiation therapy, docetaxel and doxorubicin. Five individuals (50%) were alive and cancer-free having been followed for more than 32 months (range 32-89 months). The median overall Kaplan–Meier survival was 60 months. However, a 2010 single institution feasibility study by Kawada, consisting of seven cases of ATC treated with docetaxel monotherapy, reported a less encouraging response rate of only 14% for treatment of advanced ATC.
The American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer (2012) include the following treatment recommendation:
The use of cytotoxic chemotherapy involving some combination of taxane (paclitaxel or docetaxel), and/or anthracyclines (doxorubicin) and/or platin (cisplatin or carboplatin) therapy should be considered in combination with radiation therapy or altered fractionated radiotherapy in good performance status patients with nonmetastatic ATC who desire aggressive therapy.
Strength of Recommendation: Strong
Quality of Evidence: Moderate
The NCCN Thyroid Carcinoma Guideline (V1.2016) and NCCN Drugs and Biologics Compendium (2017) include 2A recommendations for the use of docetaxel in combination with doxorubicin for the treatment of anaplastic thyroid carcinoma.
Uterine neoplasms include endometrial carcinoma and uterine sarcoma. Adenocarcinoma of the endometrium (also known as endometrial carcinoma or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. Uterine sarcomas are less common and account for only about 3% of uterine neoplasms (Koh, 2014). Several phase II clinical trials (Nomura, 2011; Pautier, 2014) have demonstrated efficacy of chemotherapeutic regimens containing docetaxel when used as treatment for endometrial carcinomas and uterine sarcomas.
The NCCN Uterine Neoplasms Guideline (V1.2017) includes category 2A recommendations for the combination of docetaxel and gemcitabine as treatment for uterine sarcomas and the combination of docetaxel and carboplatin in women with endometrial cancer in whom paclitaxel is contraindicated. NCCN also strongly encourages participation in clinical trials for uterine sarcomas endometrial cancer.
Docetaxel has also been investigated for other uses, including anal carcinoma (Kim, 2014); metastatic colorectal cancer (Sternberg, 1994) and pancreatic cancer (Saif, 2010). The most recent and promising of these studies was a small case series by Kim (2014) consisting of 8 subjects with anal cancer. As such, current evidence is insufficient to support treatment with docetaxel for these uses.
Boxed warning on Taxotere drug label:
WARNING: TOXIC DEATHS, HEPATOTOXICITY, NEUTROPENIA, HYPERSENSITIVITY REACTIONS, AND FLUID RETENTION
Special alert June 2014:
The FDA is warning that docetaxel injection products contain ethanol, which may cause individuals to experience symptoms of alcohol intoxication during and after treatment.
Complete response (CR): The disappearance of all signs of cancer as a result of treatment; also called complete remission; does not indicate the cancer has been cured.
ECOG Performance Status: A scale used to determine the individual's level of functioning. This scale may also be referred to as the WHO (World Health Organization) or Zubrod score which is based on the following scale:
|0||Fully active, able to carry on all pre-disease performance without restriction|
|1||Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work|
|2||Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours|
|3||Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours|
|4||Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair|
Karnofsky Score: A measure of the individual's overall physical health, judged by their level of activity; the score uses the following scale:
|100%||Normal, no complaints, no signs of disease|
|90%||Capable of normal activity, few symptoms or signs of disease|
|80%||Normal activity with some difficulty, some symptoms or signs|
|70%||Caring for self, not capable of normal activity or work|
|60%||Requiring some help, can take care of most personal requirements|
|50%||Requires help often, requires frequent medical care|
|40%||Disabled, requires special care and help|
|30%||Severely disabled, hospital admission indicated but no risk of death|
|20%||Very ill, urgently requiring admission, requires supportive measures or treatment|
|10%||Moribund, rapidly progressive fatal disease processes|
Line of therapy:
First-line therapy: The first or primary treatment for the diagnosis. This may include surgery, chemotherapy, radiation therapy or a combination of these therapies. Also called primary therapy and primary treatment.
Second-line therapy: Treatment given when initial treatment (first-line therapy) is not effective or there is disease progression.
Third-line therapy: Treatment given when both initial (first-line therapy) and subsequent treatment (second-line therapy) are not effective or there is disease progression.
Partial response (PR): A decrease in the size of a tumor, or in the amount of cancer in the body, resulting from treatment. Also called partial remission.
Taxane: A type of drug that blocks cell growth by stopping mitosis (cell division). Taxanes interfere with microtubules (cellular structures that help move chromosomes during mitosis). They are used to treat cancer. A taxane is a type of mitotic inhibitor and a type of antimicrotubule agent. (NCI, 2016)
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
|Revised||05/04/2017||Medical Policy & Technology Assessment Committee (MPTAC) review.|
|Revised||05/03/2017||Hematology/Oncology Subcommittee review. Formatting updated in Clinical Indication section. Updated indications in Medically Necessary statement for bladder and ovarian cancer. Added indication to Medically Necessary statement for thyroid carcinoma. Updated Coding, Discussion and References sections.|
|Revised||05/04/2016||Hematology/Oncology Subcommittee review. Description, Discussion, Definition and Reference sections updated. Brand name removed from clinical indications section. Title updated to include Docefrez. Removed ICD-9 codes from Coding section.|
|Reviewed||05/06/2015||Hematology/Oncology Subcommittee review. Discussion and Reference sections updated.|
|New||11/12/2014||Hematology/Oncology Subcommittee review. Initial document development.|