Gynecologic Oncology Disease Site Group. Effective: May 2010

Transcription

1 Practice Guideline: Systemic Therapy Summary First- or Second-Line Treatment of Metastatic or Locally Advanced Uterine Leiomyosarcoma with Fixed-Dose Rate Gemcitabine and Docetaxel (GYNE Gemcitabine + Docetaxel MET) Gynecologic Oncology Disease Site Group Effective: May 2010 Updated: April 2015

2 Systemic Therapy Summary 2 ACKNOWLEDGEMENT AND SPONSORSHIP DISCLAIMERS There are no relevant conflicts of interest to disclose. and Docetaxel p. 2

3 Systemic Therapy Summary 3 Preface This document has been prepared by the Winnipeg Regional Health Authority/CancerCare Manitoba (WRHA/CCMB) Oncology Pharmacotherapeutic (P&T) Subcommittee s Systemic Therapy Summaries Working Group, as a means of disseminating drug information and formulary decisions made by the Subcommittee. The CCMB Provincial Pharmacy Program, Provincial Oncology Drug Program (PODP) and Clinical Practice Guidelines Initiative (CPGI) have contributed to the development of this summary. Systemic Therapy Summaries (STS) are being developed for drugs/or indications where the P&T Subcommittee, based on scientific data, has accepted clinical benefit. The P&T Subcommittee Chair and the CPGI Lead/Advisory Panel Chair approve all STS documents. The content of this STS was in large part adapted from the Formulary Addition Request submitted to the P&T Subcommittee by the CCMB Gynecologic Oncology (GYNE) Disease Site Group (DSG), May This document will be reviewed, and updated as necessary, once in every twelve-month period; unless emerging evidence from scientific research dictates otherwise. Purpose This document is intended as a guide to facilitate the safe and effective clinical use of fixed-dose rate gemcitabine and docetaxel in the first-line or second-line treatment of metastatic or locally advanced uterine leiomyosarcoma. For this purpose, it may be used by qualified and licensed healthcare practitioners involved with the care of oncology patients, which may include (but is not limited to): physicians, nurses, and pharmacists at CancerCare Manitoba, Community Cancer Programs Network (CCPN) sites and WRHA Community Oncology Program sites. Disclaimer Use of this document should not preclude the practitioner s independent clinical judgment, nor should it replace consultation with the oncologist. It is the responsibility of the practitioner to develop an individualized treatment plan for each patient under his/her care, and ideally this should take place within the context of a multidisciplinary team. The unique needs and preferences of the patient and the family should always be reflected in the plan of care. This document is not a comprehensive drug monograph. Practitioners must refer to other sources for complete drug information. and Docetaxel p. 3

4 Systemic Therapy Summary 4 First- or Second-Line Treatment of Metastatic or Locally Advanced Uterine Leiomyosarcoma with Fixed-Dose Rate Gemcitabine and Docetaxel Protocol Code: GYNE Gemcitabine + Docetaxel MET Developed by: Gynecologic Oncology Disease Site Group Date of Presentation to P&T Subcommittee: May 18, 2010 Treatment Recommendation The Gynecologic Oncology DSG recommends fixed-dose rate gemcitabine in combination with docetaxel for firstor second-line treatment of metastatic or locally advanced uterine leiomyosarcoma in patients who meet the inclusion criteria (see below). Treatment Intent Non-curative Prolongation of progression-free survival (PFS) and overall survival (OS) Rationale Leiomyosarcoma of the uterus is a rare disease with a poor prognosis, accounting for about 1% of all uterine malignancies. Unfortunately, it is an aggressive disease often affecting younger patients, with peak incidence between the ages of years. 1 Current treatment options for recurrent or advanced uterine leiomyosarcoma are limited. Many single-agents and doxorubicin-based combination chemotherapy regimens have been studied in phase II trials; however, study design limitations hinder the applicability of available research and challenge any attempt to make evidence-based recommendations Docetaxel in combination with gemcitabine is considered the standard of care in many centers for the treatment of recurrent or advanced leiomyosarcoma, primarily based on the higher response rates as compared to other regimens studied in the treatment of this disease. and Docetaxel p. 4

5 Systemic Therapy Summary 5 Clinical Benefit (Level IIa Evidence see Appendix I) Two phase II studies demonstrated a high objective response rate in patients with advanced, unresectable uterine leiomyosarcoma treated with fixed-dose rate gemcitabine in combination with docetaxel. 2,3 In both studies, participants were limited to those with measurable disease having received no prior chemotherapy or treatment with one cytotoxic regimen only. Objective response of 35.8% in the first-line study compares favorably to the 20-30% response rates observed with single-agent doxorubicin, which is considered by many to be the current treatment standard. 1 PFS was 59.5% and 40.5% at 12 weeks and 24 weeks, respectively, which may be a more important endpoint. 2 An objective response of 27% in the second-line trial is the highest to date in studies of this patient population. 4 PFS at 12 weeks and 24 weeks was 73% and 52%, respectively. 3 Patient Population and Selection Criteria Inclusion criteria In combination with docetaxel (as fixed-dose gemcitabine), for the first- or second-line treatment of patients with: o o o Metastatic or locally advanced uterine leiomyosarcoma; AND An Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 (see Appendix II); AND Adequate bone marrow, renal and hepatic function CCMB Formulary Status 1. Formulary definition Restricted* * Approved and funded by CCMB, provided that criteria for use are met and request is adjudicated by DSG Chair or other designate as specified. 2. Adjudication process Complete Restricted Drug Form GYNECOLOGIC DSG (J:\Pharmacy\FORMS) Approval granted by: Gynecologic Oncology DSG Chair or Designate Repeat imaging required after 3 cycles of therapy to document disease stability or response; if patients respond or are stable, treatment may be continued for an additional 2 months and Docetaxel p. 5

6 Systemic Therapy Summary 6 Implementation and Safety Considerations Notify physician before administering full doses of chemotherapy if platelets less than 75 x 10 9 /L or absolute neutrophil count (ANC) less than 1.2 x 10 9 /L Monitor heart rate and blood pressure every 15 minutes during docetaxel treatment Observe patient for 1 hour after docetaxel administration Patients having received prior pelvic radiation should start treatment with a 25% dose reduction Treatment Regimen GYNE Gemcitabine + Docetaxel MET 1 cycle = 21 days (planned treatment until disease progression) Drug Dose CCMB Administration Guideline Gemcitabine 900 mg/m 2 on Days 1, 8 IV in normal saline (NS) 250 ml at fixed-dose rate of 10 mg/m 2 /min run over 90 minutes Docetaxel 100 mg/m 2 on Day 8 IV in NS 250 ml* over 1 hour (non-pvc bag and tubing) *use 500 ml of NS if dose greater than or equal to 200 mg NOTE: Patients having received prior pelvic radiation should start treatment with a 25% dose reduction. and Docetaxel p. 6

7 Systemic Therapy Summary 7 Pre-Medications and Supportive Care Drugs should be administered in the following order: Drug Dose CCMB Administration Guideline Metoclopramide 20 mg on Days 1, 8 Orally 30 minutes before chemotherapy* Gemcitabine (See above) (See above) Dexamethasone 8 mg on Days 7, 8, 9 Orally, twice daily; 24 hours before docetaxel treatment Outpatient prescription (Qty: 12 x 4 mg tablets) Docetaxel (See above) (See above) *An additional outpatient prescription can be written for mg to be taken orally q4h prn for breakthrough nausea and vomiting (Quantity: 60 x 10 mg tablets) and Docetaxel p. 7

8 Systemic Therapy Summary 8 Clinical Monitoring and Follow-Up Recommendations Hematology, chemistry and required tests Before each cycle: o Complete blood count (CBC) with differential, serum creatinine, urea, bilirubin, AST, ALT, alkaline phosphatase, sodium, potassium, chloride Day 8 chemotherapy: o CBC with differential Clinical toxicity assessment (see Appendix III) Prior to each cycle: o Perform physical examination including assessment for hypersensitivity, nerve damage, nausea and vomiting, diarrhea, stomatitis, skin toxicity, infection, edema, nail changes and pulmonary symptoms Assessment of treatment response Baseline imaging: CT scan of the chest, abdomen and pelvis should be obtained within 4 weeks of starting therapy CT imaging should be repeated every 3 cycles (or 2 months) to document disease stability or response Patients should be continued on treatment until time of disease progression or unacceptable toxicity and Docetaxel p. 8

9 Systemic Therapy Summary 9 Common or Clinically Important Adverse Events* (Refer to individual drug monographs for full details of adverse events) Myelosuppression 3,4,8 Myelosuppression is the primary toxicity of the regimen. Hematologic toxicities reported in phase II trials of fixed-dose rate gemcitabine plus docetaxel are as follows: Neutropenia (5-15% Grade 3; 0-12% Grade 4) Thrombocytopenia (4-29% Grade 3; 3-10% Grade 4) Anemia (9-24% Grade 3; 0-4% Grade 4) Febrile neutropenia (0-9% Grade 3; 0-6% Grade 4.7) Fever or other evidence of infection must be assessed and treated promptly Hypersensitivity reactions 5-7 Hypersensitivity reactions are observed with docetaxel treatment. The incidence of hypersensitivity reactions with docetaxel is 21% (4% severe). Reactions are most likely to occur during the first two cycles of docetaxel treatment, generally within the first few minutes after the infusion is started Reactions should be managed according to the CCMB standing order Hypersensitivity Reaction Treatment for Taxanes Fluid retention 5-7 Docetaxel-induced fluid retention occurs in 52% of patients receiving dexamethasone pre-medication, and in 82% of patients without pre-medication. This includes edema, and less frequently, pleural effusion, ascites, pericardial effusion and weight gain. It usually begins at the lower extremities and may become generalized with a weight gain of 3 kg or more. Fluid retention is not accompanied by acute episodes of dehydration, oliguria or hypotension Fluid accumulation is due to increased capillary permeability rather than hypoalbuminemia or cardiac, hepatic or renal damage. It is slowly reversible after treatment is discontinued (median 29 weeks). However, early, aggressive diuretic treatment may occasionally be required. Antihistamines have not been shown to be useful in controlling fluid retention Gastrointestinal Emetogenic potential of regimen = low (10-30%) toxicities 2-4,8,9 The more common gastrointestinal toxicities include nausea and vomiting, stomatitis and diarrhea Phase II trials of fixed-dose rate gemcitabine plus docetaxel reported a 4-9% range for Grade 3 gastrointestinal toxicities and 0-3% range for Grade 4 toxicities and Docetaxel p. 9

10 Systemic Therapy Summary 10 Neuropathy 5-7 Neuropathy is a potential adverse event of docetaxel treatment. Rarely, neurologic effects result in moderate to severe neuropathy, leading to decreased dexterity and/or disturbances in gait, usually after cumulative doses of 600 mg/m 2 Alopecia 5-7 Docetaxel causes hair loss in most patients, characterized by sudden onset around days after treatment has begun Skin rash 5-7 Docetaxel can cause cutaneous reactions characterized by a rash, including localized eruptions mainly on feet and hands, but also on arms, face or thorax. These reactions are observed in 48% of patients, and are occasionally associated with pruritus. Eruptions generally occur within one week following the docetaxel infusion which resolve before the next infusion, and are not disabling Skin rash can also be caused by gemcitabine. Typically mild to moderate in severity, the rash appears as macular or finely granular maculopapular pruritic eruptions on the trunk and extremities. It is not dose-limiting and usually responds to topical corticosteroids or oral antihistamines (e.g., diphenhydramine) if needed Nail changes 5 Docetaxel-induced nail toxicities include characteristic changes such as: nail discoloration, splinter hemorrhage, subungual hematoma, hyperkeratosis, Beau-Reil lines and acute paronychia. Less frequently, nail loosening (onycholysis) and nail loss (onychomadesis) occur. Incidence of Grade 1/2 changes has been reported as 19-51%, while Grade 3/4 toxicities range from % Patients may also experience discomfort or pain, and nail bed infection is a potential complication. Changes usually subside after cessation of docetaxel, but may occasionally persist Hand-foot skin reactions 5-7 Docetaxel treatment has been associated with hand-foot skin reactions. A reaction that occurs despite dexamethasone prophylaxis may respond to administration of pyridoxine 50 mg orally three times a day Fever/flu-like symptoms 5-7 Gemcitabine treatment has been associated with flu-like symptoms which are usually mild, and short in duration. If necessary, acetaminophen may be used to manage fever Other adverse effects Fatigue of docetaxel 5-7 Asthenia Myalgia Arthralgia *See Appendix III CTCAE v.4.0 and Docetaxel p. 10

11 Systemic Therapy Summary 11 Precautions 5-7 Myelosuppression Hemolytic uremic syndrome has been reported (0.3%) with the use of gemcitabine and is characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal failure. The syndrome can present either acutely with severe hemolysis, thrombocytopenia and rapidly progressive renal failure, or more insidiously with mild or no thrombocytopenia and slowly progressive renal failure. The etiology is unknown at present. Onset of this syndrome has been observed during and shortly after gemcitabine therapy. If not treated promptly, the patient may suffer irreversible renal failure and require dialysis. Patients with impaired renal function should be monitored closely while being treated with gemcitabine. Hypersensitivity reactions Pre-treatment with dexamethasone reduces the severity of docetaxel-induced hypersensitivity reactions and cutaneous toxicity. If dexamethasone has not been taken prior to treatment, diphenhydramine 50 mg IV and dexamethasone 10 mg IV may be given 30 minutes before starting docetaxel to ameliorate hypersensitivity reactions. Patients should then be instructed to take dexamethasone 8 mg orally twice daily for two days. Docetaxel infusion must be started slowly to assess the possibility of a reaction. Start at one-third rate for the first 15 minutes, then increase. Fluid retention Patients should receive prophylactic treatment with dexamethasone 8 mg orally BID for 3 consecutive days starting the day before docetaxel administration to decrease the frequency and severity of docetaxel-induced fluid retention, and to delay its onset. Severe pulmonary toxicity Acute dyspnea is observed in approximately 8% of patients receiving gemcitabine, but is usually self-limiting. Rarely, severe pulmonary toxicities such as pulmonary edema, interstitial pneumonitis and acute respiratory distress syndrome (ARDS) have been reported. The symptoms are manifested as progressive dyspnea, tachypnea, hypoxemia and pulmonary infiltrates on chest radiograph that are sometimes accompanied by fever and cough. Toxicities usually occur after several cycles of gemcitabine, but have also been seen as early as the first cycle. Discontinue if drug-induced pneumonitis is suspected. Liver impairment Patients are at a higher risk of developing severe adverse reactions to docetaxel if they have elevated transaminase (ALT and/or AST) and alkaline phosphatase. Liver impairment reduces clearance and increases systemic exposure to docetaxel (see Dose Modifications). and Docetaxel p. 11

12 Systemic Therapy Summary 12 Dose Modifications* *(adapted from the BCCA Drug Manual and Protocol Summary) 5-7 Hematological toxicity For Day 1 Blood Counts* Gemcitabine Dose (% full dose) ANC greater than or equal to 1.2 x 10 9 /L and platelets greater than or equal to 75 x 10 9 /L 100% Grade 4 febrile neutropenia with previous cycle or Greater than 2 week delay of the start of next cycle due to toxicity 75% *Do not start new cycle until ANC greater than 1.2 x 10 9 /L and platelets greater than 75 x 10 9 /L For Day 8 Blood Counts Gemcitabine Dose (% full dose) Docetaxel Dose (% full dose) ANC greater than or equal to 1.2 x 10 9 /L and platelets greater than or equal to 75 x 10 9 /L 100% 100% ANC less than 1.2 x 10 9 /L or platelets less than 75 x 10 9 /L Hold therapy and consider starting G-CSF secondary prophylaxis or Decrease to 75% Hold therapy and consider starting G-CSF secondary prophylaxis or Decrease to 75% Non-hematological toxicity (except neurotoxicity Grade (see Appendix III) Percent of Previous Cycle Docetaxel and Day 1 Gemcitabine Dose and Docetaxel p. 12

13 Systemic Therapy Summary 13 and hepatotoxicity) 0-2 (except nausea and vomiting or alopecia) 100% 3 (except nausea and vomiting or alopecia) 75% or hold (at discretion of treating physician) 4 50% or hold (at discretion of treating physician) Grade 2 neurotoxicity Symptomatic weakness, sensory alteration or paresthesia (including tingling) Grade (see Appendix III) Percent of Previous Cycle Docetaxel Any occurrence 75% Recovery to grade less than or equal to 1 50% No recovery to grade less than or equal to 1 Hold therapy until symptoms less than or equal to grade 1 Discontinue docetaxel therapy if symptoms do not resolve within 6 weeks Grade 3 neurotoxicity Weakness, sensory alteration or paresthesia Grade (see Appendix III) Percent of Previous Cycle Docetaxel and Docetaxel p. 13

14 Systemic Therapy Summary 14 Any occurrence Hold docetaxel therapy until symptoms less than or equal to grade 1 toxicity Discontinue docetaxel therapy if symptoms do not resolve within 6 weeks Recovery to grade less than or equal to 1 Reinstitute dose at 50% (physician may escalate dose at own discretion) No recovery to grade less than or equal to 1 Discontinue docetaxel Renal dysfunction Dose (mg/m 2 ) Gemcitabine Although evidence indicates gemcitabine is not nephrotoxic, care should be exercised in the use of the agent in patients with renal dysfunction, as risk of developing hemolytic uremic syndrome may be increased in this group. Patients with renal dysfunction should be monitored closely while being treated with gemcitabine Docetaxel No dose adjustment required Hepatic dysfunction Dose (mg/m 2 ) Gemcitabine Use with caution in patients with mild to moderate hepatic impairment; consider dose reduction or discontinuation in patients with severe impairment Docetaxel alkaline phosphatase less than 2.5 x ULN* 100 and Docetaxel p. 14

15 Systemic Therapy Summary 15 and AST and/or ALT less than 1.5 x ULN alkaline phosphatase 2.5 to 6 x ULN and AST and/or ALT 1.5 to 3.5 x ULN 75 alkaline phosphatase greater than 6 x ULN and AST and/or ALT greater than 3.5 x ULN 0 *ULN = upper limit of normal Clinical Considerations Docetaxel is contraindicated in patients who have a history of hypersensitivity to docetaxel or other drugs formulated with polysorbate 80. Patients who previously reacted to paclitaxel may also react to docetaxel therapy. When docetaxel is used in patients who abuse alcohol, or have abused alcohol, the risk of severe neurotoxic reactions may be increased. and Docetaxel p. 15

16 Systemic Therapy Summary 16 References 1. Fleming G. Gemcitabine/docetaxel-Welcome to a new standard. Gynecol Oncol 2008;109(3): Hensley ML, Blessing JA, Mannel R, et al. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol 2008;109(3): Hensley ML, Blessing JA, DeGeest K, et al. Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study. Gynecol Oncol 2008;109(3): Hensley ML, Ishill N, Soslow R, et al. Adjuvant gemcitabine plus docetaxel for completely resected stages I-IV high grade uterine leiomyosarcoma: results of a prospective study. Gynecol Oncol 2009;112(3): British Columbia Cancer Agency. Cancer Drug Manual, Docetaxel Drug Monograph. Last updated December [Last accessed 14 March 2011]. 6. British Columbia Cancer Agency. Cancer Drug Manual, Gemcitabine Drug Monograph. Last updated March [Last accessed 14 March 2011]. 7. British Columbia Cancer Agency. Protocol Summary: Treatment of Uterine Sarcoma Cancer Using Docetaxel and Gemcitabine. Last updated January [Last accessed 14 March 2011]. 8. Hensley ML, Maki R, Venkatraman E, et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol 2002;20(12): Hesketh PJ. Drug therapy: chemotherapy-induced nausea and vomiting. N Engl J Med 2008;358(23): and Docetaxel p. 16

17 Systemic Therapy Summary 17 CCMB Contributors Dr. Erin Dean, Gynecologic Oncologist, Gynecologic Oncology Disease Site Group Chair (2015) Dr. Shaundra Popowich, Obstetrician and Gynecologist, Gynecologic Oncology Disease Site Group Ms. Kimberly Watkinson, BSc (Pharm), Provincial Oncology Drug Program Contact Physician Dr. Shaundra Popowich, Obstetrician and Gynecologist, Gynecologic Oncology Disease Site Group Approved By Dr. Ralph PW Wong, Medical Oncologist Chair, WRHA/CCMB Oncology Pharmacotherapeutic Subcommittee Dr. Vallerie Gordon, Medical Oncologist Lead and Advisory Panel Chair, CCMB Clinical Practice Guidelines Initiative We gratefully acknowledge the support of CancerCare Manitoba, the CancerCare Manitoba Foundation and the Provincial Oncology Clinical Practice Guidelines Initiative and Docetaxel p. 17

18 Systemic Therapy Summary 18 Appendix I Levels of Evidence Ia Evidence obtained from meta-analysis of randomised controlled trials Ib Evidence obtained from at least one randomised controlled trial IIa Evidence obtained from at least one well-designed controlled study without randomisation IIb Evidence obtained from at least one other type of well-designed, quasi- experimental study III Evidence obtained from well-designed, non-experimental descriptive studies, such as comparative studies, correlation studies and case studies IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities British Committee for Standards in Haematology and Docetaxel p. 18

19 Systemic Therapy Summary 19 Appendix II ECOG Performance Status Scale 0 Fully active, able to carry on all pre-disease activities without restriction (Karnofsky ) 1 Restricted in physical strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, for example, light housework or office work (Karnofsky 70-80) 2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about greater than or equal to 50% of waking hours (Karnofsky 50-60) 3 Capable of only limited self-care, confined to bed or chair greater than or equal to 50% of waking hours (Karnofsky 30-40) 4 Completely disabled, cannot carry on any self-care, totally confined to bed or chair (Karnofsky 10-20) Oken MM, Creech RH, et al. Toxicity and Response Criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5: , Eastern Cooperative Oncology Group Robert Comis M.D., Group Chair and Docetaxel p. 19

20 Systemic Therapy Summary 20 Appendix III Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Publish Date: 18 May 2009 Grades Grade refers to the severity of the AE. The CTCAE displays grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age- appropriate instrumental ADL*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. A semi-colon indicates or within the description of the grade. A single dash (-) indicates a grade is not available. Not all grades are appropriate for all AEs. Therefore, some AEs are listed with fewer than five options for grade selection. Grade 5: Grade 5 (Death) is not appropriate for some AEs and therefore is not an option Activities of Daily Living (ADL): * Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. ** Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. CTCAE document available at: [Accessed 10 September 2010] and Docetaxel p. 20

21 Systemic Therapy Summary 21 Appendix IV FIGO Staging for Uterine Sarcomas Leiomyosarcoma Stage Definition I IA Tumour limited to uterus < 5 cm IB Tumour limited to uterus > 5 cm II IIA Tumour extends to the pelvis, adnexal involvement IIB Tumour extends to extra-uterine pelvic tissue III IIIA Tumour invades abdominal tissues, one site IIIB More than one site IIIC Metastasis to pelvic and/or para-aortic lymph nodes IV IVA Tumour invades bladder and/or rectum IVB Distant metastasis Adapted from the International Federation of Gynecology and Obstetrics Committee, FIGO Staging for Uterine Sarcomas. AccessMedicine McGraw-Hill 2010 The McGraw-Hill Companies. [Accessed 10 March 2011]. and Docetaxel p. 21

22 Systemic Therapy Summary 22 CancerCare Manitoba 675 McDermot Avenue Winnipeg, Manitoba, Canada R3E 0V9 CCMB STS: GYNE Gemcitabine + Docetaxel MET May 2010 Effective: May 2010 Updated: April 2015 CancerCare Manitoba, May All rights reserved. This material may be freely reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organization, or for commercial purposes is allowed without written permission of CancerCare Manitoba. and Docetaxel p. 22