Chapter 10: Endometrial Cancer

Maurie Markman

INTRODUCTION

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Epidemiology

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Epidemiology

Incidence:

52,630 (Estimated new cases for 2014 in the United States)

Stage at Presentation

Localized:

72%

Stage I:

79%

24.3 per 100,000 women per year.

Regional:

16%

Stage II:

12.5%

Deaths:

Estimated 8,590 in 2014

Distant:

Stage III:

13.3%

Median age at diagnosis:

62 years

Unstaged:

Stage IV:

Modified from Creasman WT et al. J Epidemiol Biostat 2001;6:47–86

Siegel R et al. CA Cancer J Clin 2014;64:9–29

Surveillance, Epidemiology and End Results (SEER) Program, available from http://seer.cancer.gov (accessed in 2013)

Pathology

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Pathology

Endometrioid

Ciliated adenocarcinoma
Secretory adenocarcinoma
Adenocarcinoma with squamous differentiation–Adenosquamous

75–80%

Serous

<10%

Clear cell

Mucinous

Squamous

<1%

Mixed

10%

Undifferentiated

Kurman RJ, Ellenson LH, Ronnett BM editors. Blaustein's Pathology of the Female Genital Tract. 6th ed: Springer; 2011

Work-up

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Work-up

Stage I

H&P

CBC with platelet count

Chest x-ray

Cervical cytology

Stage II

Consider endocervical curettage or cervical biopsy

Stages III/IV

CA-125 MRI/CT as clinically indicated

Staging

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Staging

TNM Category

FIGO Stage^✫

Primary Tumor (T)

Primary tumor cannot be assessed

No evidence of primary tumor

Tis

Carcinoma in situ (preinvasive carcinoma)

Tumor confined to corpus uteri

T1a

Tumor limited to endometrium or invades less than one-half of the myometrium

T1b

Tumor invades one-half or more of the myometrium

Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus^†

T3a

IIIA

Tumor involves serosa and/or adnexa (direct extension or metastasis)

T3b

IIIB

Vaginal involvement (direct extension or metastasis) or parametrial involvement

IVA

Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4)

^✫FIGO staging no longer includes stage 0 (Tis)

^†Endocervical glandular involvement only should be considered as stage I and not stage II

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Staging

TNM Category

FIGO Stage

Regional Lymph Nodes (N)

Regional lymph nodes cannot be assessed

No regional lymph node metastasis

IIIC1

Regional lymph node metastasis to pelvic lymph nodes

IIIC2

Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes

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Staging

TNM Category

FIGO Stage

Distant Metastasis (M)

No distant metastasis (no pathologic M0; use clinical M to complete stage group)

IVB

Distant metastasis (includes metastasis to inguinal lymph nodes intraperitoneal disease, or lung, liver, or bone. It excludes metastasis to paraaortic lymph nodes, vagina, pelvic serosa, or adnexa)

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010.

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Staging

Histologic Grade (G)

Well differentiated

Moderately differentiated

G3–4

Poorly differentiated or undifferentiated

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Staging

Group

0^✫

Tis

T1a

T1b

III

IIIA

T3a

IIIB

T3b

IIIC1

T1-T3

IIIC2

T1-T3

IVA

Any N

IVB

Any T

Any N

^✫FIGO no longer includes stage 0 (Tis)

Overall 5-Year Survival: Relative to FIGO Disease Stage

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Overall 5-Year Survival: Relative to FIGO Disease Stage

Stage

% Survival

88.9

80.7

IIa

79.9

IIb

72.3

IIIa

63.4

IIIb

38.8

IIIc

51.1

IVa

19.9

IVb

17.2

Expert Opinion

Over the past decade there has been considerable evolution in the management of endometrial cancer. Fortunately, the large majority of patients present with early stage disease, and in these patients surgical resection are undertaken with curative intent. Recent reports have questioned the routine use of postoperative external beam radiation therapy in patients with an intermediate risk of recurrence, and a definitive answer to the role of radiation requires further investigation

However, it is the place of cytotoxic chemotherapy in the treatment of advanced, metastatic, and recurrent endometrial cancer that has undergone the greatest change. Once considered a relatively chemoresistant malignancy, it is now recognized that objective responses can be observed in ≥50% of patients with measurable disease^1,2 following treatment with several combination chemotherapy regimens including:

A number of single agents have documented activity (>15–20% objective response rates) in this malignancy including:

Unfortunately, because of the relative rarity of metastatic endometrial cancer, there have been no phase III trials directly comparing the utility of these individual drugs that might help guide routine clinical management

Older randomized trials had revealed the potential for combination chemotherapy to improve objective response rates and progression-free survival in metastatic or recurrent endometrial cancer. The Gynecologic Oncology Group (GOG) 177 trial established doxorubicin + cisplatin followed by paclitaxel (TAP) as the standard for systemic treatment of stage III-IV and recurrent endometrial cancer.¹ However, TAP was associated with substantially more toxicity compared than the comparator arm, doxorubicin + cisplatin (AP). G2/3 neurotoxicity in 39% of patients who received TAP compared with 5% of those given AP, and 24% of patients who received TAP discontinued treatment because of toxicities compared with 9% of patients who received AP. As a result, TAP often was not utilized

An earlier report suggested the activity of a paclitaxel + carboplatin (TC) combination without doxorubicin might be similar to TAP but with less toxicity.^2,3 The TC combination had a high objective response rate in endometrial cancer and a relatively favorable side-effect profile. These results provided the rationale for GOG 209, in which TAP and TC were compared in 1300 women with advanced or recurrent endometrial cancer. Patients were randomly assigned to receive either:

TAP: Doxorubicin 45 mg/m² + cisplatin 50 mg/m² (day 1), followed by paclitaxel 160 mg/m² (day 2) every 21 days with hematopoietic growth factor support for a maximum of 7 cycles, or
TC: Paclitaxel 175 mg/m² + carboplatin AUC = 6 mg/mL/min (day 1) every 21 days for a maximum of 7 cycles
- Paclitaxel 135 mg/m² and carboplatin AUC = 5 mg/mL/min were given to women with a history of pelvic/spine irradiation

Designed as a noninferiority trial, the study had 2 primary objectives:

Determine whether TC was therapeutically equivalent (noninferior) to TAP with respect to overall survival
Determine whether TC has a more favorable toxicity profile

A test for homogeneity suggested a consistent effect of treatment with TC across all prespecified subgroups. At interim analysis the authors concluded: “TC is not inferior to TAP in terms of PFS and OS….Overall, the toxicity profile favors TC. Thus, TC as prescribed in this study is an acceptable backbone for further trials in combination with ‘targeted’ therapies.”

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GOG 209 Interim Analysis

Miller D et al. Randomized phase III noninferiority trial of first-line chemotherapy for metastatic or recurrent endometrial carcinoma: a Gynecologic Oncology Group study [abstract]. Gynecol Oncol 2012;125:771

TAP

Interim Efficacy Analysis

PFS

14 months

HR = 1.03

38 months

32 months

HR = 1.01

Safety/Tolerability

Discontinued therapy for toxicity^✫

17.6%

11.9%

Neutropenia and fever

P = 0.01

G1 sensory neuropathy

26%

19%

P <0.01

G3/4 thrombocytopenia

22.8%

12.8%

P <0.001

G3/4 neutropenia

52.1%

79.7%

P < 0.001

G3/4 other hematologic

30.6%

21.2%

P <0.001

G3/4 nausea

8.9%

5.6%

P = 0.024

G3/4 vomiting

7.0%

3.5%

P = 0.006

G3/4 diarrhea

5.7%

2.0%

P <0.001

G3/4 stomatitis

1.3%

0.2%

P = 0.019

G3/4 creatinine elevation

1.9%

0.6%

P = 0.044

TAP = Doxorubicin + cisplatin, followed by paclitaxel with growth factor support.

TC = paclitaxel + carboplatin

^✫About two-thirds of patients in each group completed 7 planned cycles, and another 10% completed 6 cycles. The most common reason for discontinuation was completion of protocol specified therapy

It should also be noted that a combination chemotherapy regimen (cisplatin + doxorubicin) has been demonstrated in a phase III trial to improve survival compared to whole abdominal radiotherapy when employed as initial treatment following surgical cytoreduction in women with stage III and IV (maximum 2-cm residual disease) endometrial cancer.⁴ Based on existing data, many clinicians currently elect to employ 4–6 cycles of systemic chemotherapy, followed by local pelvic radiation in women whose major disease manifestations are principally confined to the pelvic region. The intent of the radiation is to reduce the risk of disease local recurrence in this specific clinical setting. Future randomized trials will hopefully define the utility of a combined chemotherapy-plus-radiotherapy approach in advanced and metastatic endometrial cancer

Certain subpopulations of endometrial cancer have long been known to be responsive to therapy with progesterone.⁵ Clinical features that would predict for a patient who may respond to this treatment option include:

Low-grade cancer (grade 1)
Evidence of progesterone receptors within the primary tumor specimen
Long disease-free interval (eg, >1–2 years) between the diagnosis of endometrial cancer and documented disease recurrence
Nonvisceral metastatic disease

Perhaps the single most important factor to consider in this setting is tumor grade. Patients with high-grade endometrial cancers are unlikely to respond to hormonal manipulation. Conversely, it may be quite reasonable to initially attempt to treat a patient with a low-grade metastatic endometrial cancer with progesterone before administering chemotherapy

Summary:

Primary treatment for localized (stages I, II) endometrial cancer is surgery. In appropriately selected patients, postoperative radiation is delivered to reduce the risk of local relapse. For patients unable to undergo surgery (eg, significant preexisting cardiac dysfunction), external beam radiation therapy may substitute as the primary treatment modality
In stage III, stage IV, or recurrent endometrial cancer, the current “standard-of-care” should be considered combination chemotherapy following an attempt at optimal surgical resection (principally in the stage III setting). The regimen-of-choice remains to be defined, but options include cisplatin + doxorubicin + paclitaxel, carboplatin + paclitaxel, or cisplatin + doxorubicin
Patients unable to receive combination chemotherapy (eg, secondary to clinically relevant preexisting comorbidity) may be treated with one of several previously noted cytotoxic agents with known biological activity in metastatic endometrial cancer
In carefully selected patients (criteria described above), prior to the delivery of cytotoxic chemotherapy, treatment with a progesterone agent may reasonably be attempted

REGIMEN FOR ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA: DOXORUBICIN + CISPLATIN (AC)

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Regimen for Advanced or Recurrent Endometrial Carcinoma: Doxorubicin + Cisplatin (AC)

Randall ME et al. J Clin Oncol 2006;24:36–44

Prehydration for cisplatin: ≥1000 mL 0.9% sodium chloride injection (0.9% NS) by intravenous infusion over 2 hours

Note: Encourage patients to increase oral intake of non-alcoholic fluids, and provide electrolyte replacement as needed (potassium, magnesium, sodium)

Doxorubicin 60 mg/m²; administer by slow intravenous injection over 3–5 minutes on day 1, every 21 days (total dosage/cycle = 60 mg/m²)

Maximum allowable total cumulative lifetime doxorubicin dosage = 420 mg/m²; that is, no more than 7 repeated treatment cycles
Doxorubicin may be given during hydration for cisplatin

Cisplatin 50 mg/m²; administer intravenously in 250 mL 0.9% NS over 1 hour after doxorubicin on day 1, every 21 days (total dosage per cycle = 50 mg/m²)

Supportive Care

Antiemetic prophylaxis

Emetogenic potential: HIGH. Potential for delayed symptoms

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis may be indicated

See Chapter 43 for more information

Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

Antimicrobial primary prophylaxis to be considered:

Antibacterial—not indicated
Antifungal—not indicated
Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Treatment Modifications

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Treatment Modifications

Adverse Event^✫

Dose Modification

Doxorubicin 60 mg/m² and

ANC <1500/mm³ or platelet count <100,000/mm³

Reduce doxorubicin dosage to 45 mg/m^2†

Doxorubicin 45 mg/m² and

ANC <1500/mm³ or platelet count <100,000/mm³

Reduce doxorubicin dosage to 30 mg/m^2†

Doxorubicin 30 mg/m² and

ANC <1500/mm³ or platelet count <100,000/mm³

Reduce doxorubicin dosage to 15 mg/m^2†

Doxorubicin 15 mg/m² and

ANC <1500/mm³ or platelet count <100,000/mm³

Discontinue doxorubicin

Treatment interruption caused by myelosuppression exceeding 6 weeks

Discontinue doxorubicin

Decline in cardiac ejection fraction of 20% from baseline, or development of congestive heart failure or other life-threatening cardiac problems

Discontinue doxorubicin; continue cisplatin

Serum creatinine ≥2.0 mg/dL (≥177 μmol/L)

Hold cisplatin

^✫Consider growth factor support for myelosuppression

^†Reinstitute dose if myelosuppression resolves

Patient Population Studied

A study of 422 women with stages III or IV endometrial carcinoma with a maximum of 2 cm of postoperative residual disease who were randomly allocated to receive whole abdominal radiation or doxorubicin and cisplatin

Efficacy (N = 194)

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Efficacy (N = 194)

Initial Site of Recurrence

No (%)

Pelvis

34 (18%)

Abdomen

27 (14%)

Extraabdominal or liver metastases

34 (18%)

Toxicity (N = 191)

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Toxicity (N = 191)

Adverse Events

% of Patients

Grade

Leukopenia

Neutropenia

Thrombocytopenia

Other hematologic

Maximum hematologic

Hepatic

—

Genitourinary

Cardiac

Vascular

Pulmonary

Neurologic

Pain

—

Weakness

—

Fatigue

Metabolic

Infection

Fever

Allergy

—

Dermatologic

Alopecia

NA, not available

Reason for Treatment Discontinuation (N = 194)^✫

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Reason for Treatment Discontinuation (N = 194)^✫

Percent

Completed treatment

123

63.4

Progression

9.3

Patient refusal

7.2

Toxicity

17.0

Death

2.1

Other

1.0

^✫Based on 7 cycles of doxorubicin + cisplatin followed by 1 cycle of cisplatin alone

Therapy Monitoring

Physical examination, CBC and differential count, and serum creatinine before each chemotherapy cycle
Evaluation of ejection fraction immediately before cycle 6 (or earlier, if clinically indicated)
Efficacy assessment every 2 to 3 cycles

REGIMEN FOR ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA: PACLITAXEL + CARBOPLATIN (TC)

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Regimen for Advanced or Recurrent Endometrial Carcinoma: Paclitaxel + Carboplatin (TC)

Sorbe B et al. Int J Gynecol Cancer 2008;18:803–808

Premedication for paclitaxel:

Dexamethasone 20 mg per dose; administer orally or intravenously in 10–50 mL 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) for 2 doses, 12–14 hours and 6–7 hours before starting paclitaxel

Diphenhydramine 50 mg, by intravenous injection 30 minutes before starting paclitaxel

Ranitidine 50 mg; administer intravenously over 30–60 minutes, 30 minutes before starting paclitaxel

Paclitaxel 175 mg/m²; administer intravenously in a volume of 0.9% NS or D5W sufficient to produce a solution with concentration within the range 0.3–1.2 mg/mL over 3 hours on day 1 every 3 weeks (total dosage/cycle = 175 mg/m²)

Carboplatin^✫ AUC = 5 mg/mL · min; administer intravenously in 50–150 mL D5W over 60 minutes, on day 1, every 3 weeks (total dosage/cycle calculated to produce an AUC = 6 mg/mL · min) (see equation below)

In practice, creatinine clearance (Clcr) is used in place of glomerular filtration rate (GFR). Clcr can be calculated from the equation of Cockcroft and Gault:

Note: On October 8, 2010, the U.S. Food and Drug Administration (FDA) identified a potential safety issue with carboplatin dosing based on recent changes in the measurement of serum creatinine. By the end of 2010, all clinical laboratories in the USA will use the standardized Isotope Dilution Mass Spectrometry (IDMS) method to measure serum creatinine, which could result in an overestimation of the GFR in some patients with normal renal function. A carboplatin dose calculated with an IDMS-measured serum creatinine result using the Calvert formula could exceed an expected exposure (AUC) and result in increased drug-related toxicity

Provided actual GFR measurements are made to assess renal function, carboplatin can be safely dosed according to the Calvert formula described in product labeling

If GFR (or creatinine clearance) is estimated based on serum creatinine measurements by the IDMS method, the FDA recommended for patients with normal renal function capping an estimated GFR at 125 mL/min for any targeted AUC value. No greater estimated GFR values should be used

U.S. FDA. Carboplatin dosing. [online] May 23, 2013. Available from: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm228974.htm [accessed February 26, 2014]

Calvert AH et al. J Clin Oncol 1989;7:1748–1756

Cockcroft DW, Gault MH. Nephron 1976;16:31–41

Jodrell DI et al. J Clin Oncol 1992;10:520–528

Sorensen BT et al. Cancer Chemother Pharmacol 1991;28:397–401

Supportive Care

Antiemetic prophylaxis

Emetogenic potential: HIGH. Potential for delayed symptoms

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis may be indicated

See Chapter 43 for more information

Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

Antimicrobial primary prophylaxis to be considered:

Antibacterial—not indicated
Antifungal—not indicated
Antiviral—not indicated unless patient previously had an episode of HSV

See Chapter 47 for more information

Patient Population Studied

A prospective, phase II, multicenter study evaluating carboplatin and paclitaxel in the treatment of patients with primary advanced or recurrent endometrial carcinoma. Sixty-six patients were enrolled: 18 with primary advanced tumors and 48 with recurrences. All histologic types and tumor grades were allowed

Efficacy (N = 66)

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Efficacy (N = 66)

Complete response

29%

Partial response

38%

Median progression-free survival

14 months

3-Year progression-free survival

18.2%

5-Year progression-free survival

12.5%

Median overall survival

26 months

3-Year overall survival

33.3%

5-Year overall survival

20.3%

Primary Advanced Cases (N = 18)

Complete response

50%

Partial response

33%

Median progression-free survival

14 months

Median survival

19 months

Recurrent Cases (N = 48)

Complete response

21%

Partial response

40%

Median progression-free survival

14 months

Median survival

27 months

Assessment: Clinical examination, gynecologic examination under anesthesia, transvaginal and transabdominal ultrasound, and computerized tomography were used in the evaluation of the tumor status. WHO response criteria were used to evaluate tumor

Note: Prior radiotherapy was not associated with response rate (P = 0.565), PFS rate (P = 0.420), or OS rate (P = 0.637) in this study

Toxicity (N = 66)

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Toxicity (N = 66)

Adverse Events

% of Patients

Grade (%)

Hematologic

Anemia

40.9

43.9

—

Neutropenia^✫

25.8

15.2

4.5

3.0

Thrombocytopenia

3.0

1.5

3.0

Nonhematologic

Infection/fever

—

Renal

42.2

—

Cardiac

7.6

—

Neurologic^†

37.9

31.8

13.6

—

Nausea/vomiting

39.4

16.7

4.5

1.5

^✫In 6 cases (9.1%), chemotherapy was stopped because of this toxicity

^†In 13 cases (19.7%), therapy was prematurely stopped because of this toxicity

In 2 cases, allergic reactions prohibited completion of therapy

NCI CTC, National Cancer Institute (USA) Common Toxicity Criteria, version 2.0. At: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm [accessed December 7, 2013]

Therapy Monitoring

Physical examination, CBC and serum creatinine before each chemotherapy cycle
Efficacy assessment every 2–3 cycles

Treatment Modifications

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Treatment Modifications

Adverse Event

Dose Modification

At start of a cycle ANC ≤1000/mm³ or platelet count ≤100,000/mm³

Delay start of cycle up to 2 weeks until ANC >1000/mm³ and platelet count >100,000/mm³

ANC ≤1000/mm³ or platelet count ≤100,000/mm³ for more than 2 weeks but less than 3 weeks after scheduled start of next cycle

Reduce paclitaxel and carboplatin dosages by 20% (140 mg/m² and AUC = 4, respectively)

At start of a cycle ANC ≤1000/mm³ or platelet count ≤100,000/mm³ despite dose reduction

Delay start of cycle up to 2 weeks until ANC >1000/mm³ and platelet count >100,000/mm³, then administer filgrastim or pegfilgrastim after completing chemotherapy without changing chemotherapy dosages

Serum creatinine >2 mg/dL (>177 μmol/L) or G ≥3 peripheral neuropathy

Delay start of cycle up to 2 weeks; if serum creatinine does not decrease to ≤2 mg/dL (≤177 μmol/L) or G peripheral neuropathy within that 2-week period, discontinue therapy

REGIMEN: PACLITAXEL, DOXORUBICIN, CISPLATIN (TAP)

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Regimen: Paclitaxel, Doxorubicin, Cisplatin (TAP)

Fleming GF et al. J Clin Oncol 2004;22:2159–2166

Prehydration for cisplatin: 1000 mL 0.9% sodium chloride injection (0.9% NS); administer intravenously over at least 2 hours

Notes: Encourage patients to increase oral intake of non-alcoholic fluids, and provide electrolyte replacement as needed (potassium, magnesium, sodium)

Doxorubicin may be administered during hydration for cisplatin

Doxorubicin 45 mg/m² (maximum single dose = 90 mg); administer by slow intravenous injection over 3-5 minutes on day 1 every 21 days (total dosage/cycle = 45 mg/m²; maximum dose/cycle = 90 mg)

Followed immediately afterward by:

Cisplatin 50 mg/m² (maximum single dose = 100 mg); administer intravenously in 250 mL 0.9% sodium chloride injection (0.9% NS) over 1 hour on day 1 after doxorubicin administration, every 21 days (total dosage/cycle = 50 mg/m²; maximum dose/cycle = 100 mg)

Paclitaxel 160 mg/m² (maximum single dose = 320 mg); administer by intravenous infusion in a volume of 0.9% NS or 5% dextrose injection sufficient to produce a concentration within the range of 0.3-1.2 mg/mL over 3 hours on day 2, every 21 days (total dosage/cycle = 160 mg/m²; maximum dose/cycle = 320 mg)

Notes:

No modifications to starting drug doses based on age or history of pelvic radiation therapy
Women with a BSA >2 m² received treatment as if their BSA was equal to only 2 m²

Supportive Care

Antiemetic prophylaxis

Emetogenic potential on day 1: HIGH. Potential for delayed symptoms

Emetogenic potential on day 2: LOW

See Chapter 39 for antiemetic recommendations

Hematopoietic growth factor (CSF) prophylaxis

Primary prophylaxis is indicated with one of the following:

Filgrastim (G-CSF) 5 mcg/kg per day, by subcutaneous injection, or

Pegfilgrastim (pegylated filgrastim) 6 mg/0.6 mL, by subcutaneous injection for 1 dose

Begin use from 24–72 hours after myelosuppressive chemotherapy is completed
For daily filgrastim, continue use until ANC ≥10,000/mm³ on 2 consecutive daily measurements

See Chapter 43 for more information

Antimicrobial prophylaxis

Risk of fever and neutropenia is LOW

See Chapter 47 for more information

Treatment Modifications

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Treatment Modifications

Adverse Event

Dose Modification

G3/4 thrombocy-topenia or G4 ANC

Reduce cisplatin and paclitaxel dosages by 20%

G3 peripheral neuropathy

Hold therapy until neuropathy G ≤1. Restart therapy with paclitaxel and cisplatin dosages reduced by 20%

Recurrent G3 neurologic toxicity

Discontinue therapy

LVEF <45% or a fall in LVEF ≥20% from baseline

Discontinue therapy

Toxicity-related delay in administration of >3 weeks

Discontinue therapy

Patient Population Studied

Chemotherapy-naïve women with histologically documented measurable stage III or stage IV or recurrent endometrial carcinoma of any cell type plus a GOG performance status of 0–2

Efficacy (N = 134)

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Efficacy (N = 134)

Complete response

22%

Partial response

35%

Median progression-free survival

8.3 months

Median overall survival

15.3 months

Toxicity (N = 131)

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Toxicity (N = 131)

% of Patients

Nonhematologic

Auditory

LVEF

Pulmonary

DVT

Constitutional

Vomiting

Diarrhea

Mucositis or stomatitis

Genitourinary/renal

Metabolic

Sensory neuropathy

Hematologic

Neutropenia

Thrombocytopenia

Therapy Monitoring

Every cycle: Pelvic examination and serum electrolytes, calcium, magnesium, BUN, and creatinine
Every other cycle: Tumor measurements by radiologic examination
Every third cycle: Left ventricular ejection fraction

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Chapter 10: Endometrial Cancer

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INTRODUCTION

Expert Opinion

REGIMEN FOR ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA: DOXORUBICIN + CISPLATIN (AC)

REGIMEN FOR ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA: PACLITAXEL + CARBOPLATIN (TC)

REGIMEN: PACLITAXEL, DOXORUBICIN, CISPLATIN (TAP)

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