Quick Medical Diagnosis & Treatment 2021

Ovarian Cancer & Other Tumors

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For further information, see CMDT Part 18-23: Ovarian Cancer & Ovarian Tumors

Key Features

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Essentials of Diagnosis

Symptoms include vague gastrointestinal discomfort, pelvic pressure or pain
Many cases of early-stage cancer are asymptomatic
Pelvic examination and ultrasound are mainstays of diagnosis

General Considerations

Ovarian tumors are common
Most are benign, but malignant ovarian tumors are the leading cause of death from gynecologic cancer
The wide range of types and patterns of ovarian tumors is due to the complexity of ovarian embryology and differences in tissues of origin (eTable 18–3)
Ultrasound or tumor marker screening for women with one or no affected first-degree relatives has not been shown to reduce mortality from ovarian cancer, and the risks associated with unnecessary prophylactic surgical procedures outweigh the benefits in low-risk women

eTable 18–3.Ovarian functional and neoplastic tumors.

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eTable 18–3. Ovarian functional and neoplastic tumors.

Tumor

Incidence

Size

Consistency

Menstrual Irregularities

Endocrine Effects

Potential for Malignancy

Special Remarks

Follicle cysts

Rare in childhood; frequent in menstrual years; never in postmenopausal years.

< 6 cm, often bilateral.

Moderate

Occasional

Occasional anovulation with persistently proliferative endometrium

None

Usually disappear spontaneously within 2–3 months.

Corpus luteum cysts

Occasional, in menstrual years.

4–6 cm, unilateral.

Moderate

Occasional delayed period

Prolonged secretory phase

None

Functional cysts. Intraperitoneal bleeding occasionally.

Theca lutein cysts

Occurs with hydatidiform mole, choriocarcinoma; also with gonadotropin or clomiphene therapy.

To 4–5 cm, multiple, bilateral. (Ovaries may be ≥ 20 cm in diameter.)

Tense

Amenorrhea

hCG elevated as a result of trophoblastic proliferation

None

Functional cysts. Hematoperitoneum or torsion of ovary may occur. Surgery is to be avoided.

Inflammatory (tubo-ovarian abscess)

Concomitant with acute salpingitis.

To 15–20 cm, often bilateral.

Variable, painful

Menometrorrhagia

Anovulation usual

None

Unilateral removal indicated if possible.

Endometriotic cysts

Never in preadolescent or postmenopausal years. Most common in women aged 20–40 years.

To 10–12 cm, occasionally bilateral.

Moderate to softened

Rare

None

Very rare

Associated pelvic endometriosis. Medical treatment or conservative surgery recommended.

Teratoid tumors:

Benign teratomas (dermoid cysts)

Childhood to postmenopause.

< 15 cm; 15% are bilateral.

Moderate to softened

None

Rare

Torsion can occur. Partial oophorectomy recommended.

Malignant teratomas

< 1% of ovarian tumors. Usually in infants and young adults.

> 20 cm, unilateral.

Irregularly firm

None

Occasionally, hCG elevated

All

Surgery alone may be curative.

Cystadenoma, cystadenocarcinoma

Common in reproductive years.

Serous: < 25 cm, 33% bilateral; mucinous: up to 1 cm, 10% bilateral.

Moderate to softened

None

> 50% for serous, about 5% for mucinous

Peritoneal implants often occur with serous, rarely with mucinous. If mucinous tumor is ruptured, pseudomyxoma peritonei may occur.

Endometrioid carcinoma

15% of ovarian carcinomas.

Moderate, 13% bilateral.

Firm

None

All

Adenocarcinoma of endometrium coexists in 15–30% of cases.

Fibroma

< 5% of ovarian tumors.

Usually < 15 cm.

Very firm

None

Rare

Ascites in 20% (rarely, pleural fluid).

Arrhenoblastoma

Rare. Average age 30 years or more.

Often small (< 10 cm), unilateral.

Firm to softened

Amenorrhea

Androgens —elevated

< 20%

Recurrences are moderately sensitive to irradiation.

Theca cell tumor (thecoma)

Uncommon.

< 10 cm, unilateral.

Firm

Occasional irregularity

Estrogens or androgens elevated

< 1%

Granulosa cell tumor

Uncommon. Usually in prepubertal girls or women older than 50 years.

May be very small.

Firm to softened

Menometrorrhagia

Estrogens elevated

15–20%

Recurrences are moderately sensitive to irradiation.

Dysgerminoma

About 1–2% of ovarian tumors.

< 30 cm, bilateral in 33%.

Moderate to softened

None

—

All

Very radiosensitive.

Brenner tumor

About 1% of ovarian tumors.

< 30 cm, unilateral.

Firm

None

—

Very rare

> 50% occur in postmenopausal years.

Secondary ovarian tumors

10% of fatal malignant disease in women.

Varies; often bilateral.

Firm to softened

Occasional

Very rare (thyroid, adrenocortical origin)

All

Bowel or breast metastases to ovary common.

Demographics

In women with no family history of ovarian cancer, the lifetime risk is 1.6%, whereas a woman with one affected first-degree relative has a 5% lifetime risk. With two or more affected first-degree relatives, the risk is 7%
Approximately 3% of women with two or more affected first-degree relatives will have a hereditary ovarian cancer syndrome with a lifetime risk of 40%
Women with a BRCA1 gene mutation have a 45% lifetime risk of ovarian cancer and those with a BRAC2 mutation have a 25% risk

Clinical Findings

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Symptoms and Signs

Both benign and malignant ovarian neoplasms are either asymptomatic or cause only mild nonspecific gastrointestinal or pelvic pressure symptoms
In advanced malignant disease, women may experience abdominal pain and bloating, and a palpable abdominal mass with ascites is often present

Differential Diagnosis

Benign ovarian tumor, eg, follicle cyst, corpus luteum cyst
Malignant ovarian tumor
Teratoma (usually benign)
Tubo-ovarian abscess
Endometriosis
Colon cancer
Ectopic pregnancy
Metastases to ovary, eg, gastrointestinal, breast cancers

Diagnosis

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Laboratory Tests

Serum CA 125 is elevated in 80% of women with epithelial ovarian cancer overall but in only 50% of women with early disease
Minimizing its utility in ovarian cancer screening, serum CA 125 may be elevated in premenopausal women with benign disease such as endometriosis
In premenopausal women, human chorionic gonadotropin, lactate dehydrogenase, or alpha fetoprotein, may be indicators of the type of tumor present

Imaging Studies

Transvaginal sonography (TVS) is useful for screening high-risk women but has inadequate sensitivity for screening low-risk women
Ultrasound is helpful in differentiating ovarian masses that are benign and likely to resolve spontaneously from those with malignant potential
Color Doppler imaging may further enhance the specificity of ultrasound diagnosis

Treatment

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Medications

Except for women with low-grade ovarian cancer in an early stage, postoperative chemotherapy is indicated (Table 39–3)
Several chemotherapy regimens are effective, such as the combination of cisplatin or carboplatin with paclitaxel, with clinical response rates of up to 60–70% (Table 39–13)

Table 39–3.Common cancer therapeutic agents.

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Table 39–3. Common cancer therapeutic agents.

Chemotherapeutic Agent

Usual Adult Dosage

Adverse Effects

Alkylating Agents—Nitrogen Mustards

Bendamustine (Treanda)

100–120 mg/m² intravenously every 3–4 weeks

Acute: hypersensitivity, nausea, vomiting

Delayed: myelosuppression, rash, pyrexia, fatigue

Cyclophosphamide (Cytoxan)

500–1000 mg/m² intravenously every 3 weeks; 100 mg/m²/day orally for 14 days every 4 weeks; various doses

Acute: nausea and vomiting

Delayed: myelosuppression, alopecia, hemorrhagic cystitis, cardiotoxicity (high dose)

Ifosfamide (Ifex)

1200 mg/m² intravenously daily for 5 days every 3 weeks; various doses

Acute: nausea and vomiting

Delayed: alopecia, myelosuppression, hemorrhagic cystitis, neurotoxicity

Melphalan (Alkeran)

0.25 mg/kg/day or 8–10 mg/m²/day orally for 4 days every 4–6 weeks; 16 mg/m² intravenously every 2–4 weeks; various doses

Acute: nausea, vomiting, diarrhea, hypersensitivity (intravenously)

Delayed: mucositis (intravenously), myelosuppression, increased risk of secondary malignancies

Alkylating Agents—Platinum Analogs

Carboplatin (Paraplatin)

Area under the curve (AUC)-based dosing use Calvert equation

[Dose (mg) = AUC × (GFR + 25)]

AUC = 2–7 mg/mL/min every 2–4 weeks

Acute: nausea and vomiting

Delayed: myelosuppression, electrolyte disturbances, peripheral neuropathy, nephrotoxicity, hypersensitivity

Cisplatin (Platinol)

50–100 mg/m² intravenously every 3–4 weeks; 20 mg/m²/day intravenously for 5 days every 3 weeks; various doses

Acute: nausea and vomiting

Delayed: nephrotoxicity, ototoxicity, neurotoxicity, myelosuppression, electrolyte disturbances

Oxaliplatin (Eloxatin)

85–130 mg/m² intravenously every 2–3 weeks

Acute: peripheral neuropathy exacerbated by cold, nausea, vomiting, diarrhea

Delayed: myelosuppression, elevated transaminases

Alkylating Agents—Triazenes

Dacarbazine (DTIC-Dome)

375 mg/m² intravenously on days 1 and 15 every 4 weeks; 900–1000 mg/m² intravenously over 3 to 4 days; various doses

Acute: nausea, vomiting, photosensitivity

Delayed: myelosuppression, anorexia, hypotension, flu-like syndrome

Procarbazine (Matulane)

60–100 mg/m² orally for 14 days every 4 weeks; various doses

Acute: nausea and vomiting

Delayed: myelosuppression, disulfiram-like reaction, MAO inhibition, rash

Temozolomide (Temodar)

75 mg/m² orally daily during radiation for 42 days; 150–200 mg/m² orally for 5 days every 4 weeks

Acute: nausea, vomiting, constipation

Delayed: myelosuppression, fatigue

Alkylating Agent—Miscellaneous

Chlorambucil (Leukeran)

0.1–0.2 mg/kg/day orally for 3–6 weeks; 0.4 mg/kg pulse every 4 weeks

Acute: nausea

Delayed: myelosuppression, rash

Antimetabolites—Folate Antagonists

Methotrexate (MTX; Trexall)

Intrathecal: 12 mg

High dose: 1000–12,000 mg/m² intravenously every 2–3 weeks

Acute: nausea, vomiting, mucositis

Delayed: myelosuppression, nephrotoxicity, hepatotoxicity, neurotoxicity, photosensitivity, pulmonary toxicity

Pemetrexed (Alimta)

500 mg/m² intravenously every 3 weeks

Acute: nausea, vomiting, diarrhea, rash

Delayed: myelosuppression, fatigue, mucositis

Antimetabolites—Purine Analogs

Cladribine (Leustatin)

0.1 mg/kg/day subcutaneously daily for 5 days or 0.09 mg/kg/day intravenously via continuous infusion for 7 days

Acute: nausea, injection site reaction

Delayed: myelosuppression, immunosuppression, fever, fatigue, rash

Fludarabine (Fludara)

25 mg/m² intravenously for 5 days every 4 weeks

Acute: fever, nausea, vomiting

Delayed: asthenia, myelosuppression, immunosuppression, neurotoxicity, anorexia

Mercaptopurine (6-MP; Purinethol)

Induction: 2.5–5 mg/kg/day orally

Maintenance: 1.5–2.5 mg/kg/day orally

Acute: nausea, vomiting, diarrhea, rash

Delayed: myelosuppression, immunosuppression, hepatotoxicity, mucositis

Antimetabolites—Pyrimidine Analogs

Azacitidine (Vidaza)

75–100 mg/m² subcutaneously or intravenously for 7 days every 4 weeks

Acute: injection site reaction (subcutaneously), nausea, diarrhea, fever

Delayed: myelosuppression, dyspnea, arthralgia

Capecitabine (Xeloda)

1000–1250 mg/m² orally twice a day for 14 days every 3 weeks

Acute: nausea, vomiting, diarrhea

Delayed: hand-foot syndrome, mucositis, hyperbilirubinemia, myelosuppression

Cytarabine (Ara-C, Cytosar U)

Standard dose: 100 mg/m²/day intravenously via continuous infusion for 7 days

High dose: 1000–3000 mg/m² intravenously every 12 hours for 2–6 days

Acute: nausea, vomiting, rash, flu-like syndrome

Delayed: myelosuppression

High-dose: neurotoxicity, ocular toxicities

Decitabine (Dacogen)

15 mg/m² intravenously every 8 hours for 3 days every 8 weeks; 20 mg/m² intravenously daily for 5 days

Acute: nausea, vomiting, hyperglycemia

Delayed: myelosuppression, fever, fatigue, cough

Fluorouracil (Adrucil)

400 mg/m² intravenous bolus followed by 2400 mg/m² intravenously over 46 hours every 2 weeks; 1000 mg/m² intravenously via continuous infusion for 4–5 days every 3–4 weeks; various doses

Acute: nausea, vomiting, diarrhea

Delayed: myelosuppression, hand-foot syndrome, mucositis, photosensitivity, cardiotoxicity (rare)

Gemcitabine (Gemzar)

1000–1250 mg/m² intravenously on days 1 and 8 every 3 weeks or days 1, 8, 15 every 4 weeks

Acute: nausea, vomiting, rash, flu-like symptoms, fever, diarrhea

Delayed: myelosuppression, edema, elevated transaminases

Antimicrotubules—Vinca Alkaloids

Vinblastine (Velban)

6 mg/m² intravenously on days 1 and 15 every 4 weeks; various doses

Acute: constipation

Delayed: myelosuppression, alopecia, bone pain, malaise

Vincristine (Oncovin)

0.5–1.4 mg/m² intravenously every 3 weeks; various doses; maximum single dose usually limited to 2 mg

Acute: constipation, nausea

Delayed: peripheral neuropathy, alopecia

Vinorelbine (Navelbine)

25–30 mg/m² intravenously weekly

Acute: nausea, vomiting

Delayed: myelosuppression, peripheral neuropathy, constipation, alopecia, asthenia

Antimicrotubules—Taxanes

Docetaxel (Taxotere)

60–100 mg/m² intravenously every 3 weeks

Acute: nausea, vomiting, diarrhea, hypersensitivity, rash

Delayed: myelosuppression, asthenia, peripheral neuropathy, alopecia, edema, mucositis

Paclitaxel (Taxol)

135–175 mg/m² intravenously every 3 weeks; 50–80 mg/m² intravenously weekly; various doses

Acute: diarrhea, nausea, vomiting, hypersensitivity

Delayed: myelosuppression, peripheral neuropathy, alopecia, mucositis, arthralgia

Paclitaxel protein-bound (Abraxane)

100–125 mg/m² on days 1, 8, 15 every 3–4 weeks; 260 mg/m² intravenously every 3 weeks

Acute: nausea, vomiting, diarrhea

Delayed: myelosuppression, peripheral neuropathy, alopecia, asthenia

Enzyme Inhibitors—Anthracyclines

Daunorubicin (Cerubidine)

30–60 mg/m² intravenously for 3 days

Acute: nausea, vomiting, diarrhea, red/orange discoloration of urine, infusion-related reactions (liposomal products)

Delayed: myelosuppression, mucositis, alopecia, hand-foot syndrome (liposomal doxorubicin), cardiotoxicity (dose related)

Doxorubicin (Adriamycin)

45–75 mg/m² intravenously every 3 weeks; various doses

Epirubicin (Ellence)

60–120 mg/m² intravenously every 3–4 weeks

Idarubicin (Idamycin)

10–12 mg/m² intravenously for 3 days

Liposomal doxorubicin (Doxil, Lipodox)

20–50 mg/m² intravenously every 3–4 weeks

Enzyme Inhibitors—Topoisomerase Inhibitors

Etoposide (Vepesid)

50–100 mg/m² intravenously for 3–5 days every 3 weeks

Acute: nausea, vomiting, diarrhea, hypersensitivity, fever, hypotension

Delayed: myelosuppression, alopecia, fatigue

Irinotecan (Camptosar)

180 mg/m² intravenously every other week; various doses

Acute: diarrhea, cholinergic syndrome, nausea, vomiting

Delayed: myelosuppression, alopecia, asthenia

Topotecan (Hycamtin)

1.5 mg/m² intravenously for 5 days every 3 weeks; 2.3 mg/m² orally for 5 days every 3 weeks

Acute: nausea, vomiting, diarrhea

Delayed: myelosuppression, alopecia, asthenia

Targeted Therapy—Monoclonal Antibodies

Alemtuzumab (Campath)

3–10 mg intravenously or subcutaneously three times weekly

Acute: infusion-related reaction, nausea, vomiting, hypotension, rash

Delayed: myelosuppression, immunosuppression

Atezolizumab (Tecentriq)

1200 mg intravenously every 3 weeks

Acute: infusion-related reaction

Delayed: immune-mediated reactions, fatigue, decreased appetite

Bevacizumab (Avastin)

5–15 mg/kg intravenously every 2–3 weeks

Acute: infusion-related reaction

Delayed: hypertension, proteinuria, wound healing complications, gastrointestinal perforation, hemorrhage

Cetuximab (Erbitux)

Loading dose 400 mg/m² intravenously, maintenance dose 250 mg/m² intravenously weekly

Acute: infusion-related reaction, nausea, diarrhea

Delayed: acneiform skin rash, hypomagnesemia, asthenia, paronychial inflammation, dyspnea

Daratumumab (Darzalex)

16 mg/kg intravenously weekly for weeks 1–8, every 2 weeks for weeks 9–24, and every 4 weeks from week 25 until disease progression

Acute: infusion-related reaction, nausea

Delayed: myelosuppression, fatigue, upper respiratory tract infection

Ipilimumab (Yervoy)

1–10 mg/kg intravenously every 3 weeks for a total of four doses

Acute: infusion-related reaction

Delayed: immune-related reactions, fatigue

Nivolumab (Opdivo)

240 mg intravenously every 2 weeks or 480 mg every 4 weeks

Acute: vomiting

Delayed: fatigue, musculoskeletal pain, rash, pruritus, cough, elevated transaminases

Obinutuzumab (Gazyva)

Cycle 1: 100 mg intravenously on day 1, 900 mg on day 2, 1000 mg on days 8 and 15 of a 28-day cycle; cycles 2–6: 1000 mg intravenously on day 1

Acute: infusion-related reaction, tumor lysis syndrome

Delayed: myelosuppression, pyrexia, cough, musculoskeletal disorder, potential hepatitis B reactivation

Panitumumab (Vectibix)

6 mg/kg intravenously every 2 weeks

Acute: infusion-related reaction, nausea

Delayed: acneiform skin rash, hypomagnesemia, asthenia, paronychia, fatigue, dyspnea

Pembrolizumab (Keytruda)

200 mg intravenously every 3 weeks

Acute: infusion-related reaction, nausea

Delayed: immune-mediated reactions, fatigue, cough

Pertuzumab (Perjeta)

840 mg intravenously once followed by 420 mg intravenously every 3 weeks

Acute: infusion-related reaction, diarrhea, nausea

Delayed: fatigue, alopecia, neutropenia, rash, peripheral neuropathy, cardiomyopathy

Rituximab (Rituxan)

375 mg/m² intravenously weekly for 4 weeks, or every 3–4 weeks

Acute: infusion-related reaction, tumor lysis syndrome

Delayed: lymphopenia, asthenia, rash, potential hepatitis B reactivation

Trastuzumab (Herceptin)

Initial dose 4 mg/kg intravenously, then 2 mg/kg intravenously weekly; or initial dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks

Acute: headache, nausea, diarrhea, infusion-related reaction

Delayed: myelosuppression, pyrexia, cardiomyopathy, pulmonary toxicity (rare)

Targeted Therapy—Kinase Inhibitors

Afatinib (Gilotrif)

40 mg orally once daily without food

Acute: diarrhea

Delayed: acneiform rash, stomatitis, paronychia

Alectinib (Alecensa)

600 mg orally twice daily with food

Acute: none

Delayed: myelosuppression, fatigue, edema, myalgia, dyspnea, elevated transaminases

Axitinib (Inlyta)

5–10 mg orally twice daily

Acute: diarrhea, nausea, vomiting

Delayed: hypertension, fatigue, dysphonia, hand-foot syndrome, elevated transaminases

Bosutinib (Bosulif)

500–600 mg orally once daily with food

Acute: diarrhea, nausea, vomiting

Delayed: myelosuppression, rash, abdominal pain, hepatotoxicity, fluid retention

Ceritinib (Zykadia)

740 mg orally once daily

Acute: diarrhea, nausea, vomiting

Delayed: elevated transaminases, abdominal pain, fatigue, decreased appetite

Cobimetinib (Cotellic)

60 mg orally once daily on days 1 to 21 of a 28-day cycle

Acute: diarrhea, photosensitivity reaction, nausea, vomiting

Delayed: myelosuppression, hepatotoxicity, rash, cardiomyopathy (with vemurafenib)

Crizotinib (Xalkori)

250 mg orally twice daily

Acute: nausea, vomiting, diarrhea, constipation

Delayed: vision disorder, edema, elevated transaminases, fatigue

Dabrafenib (Tafinlar)

150 mg orally twice daily without food

Acute: headache

Delayed: hyperkeratosis, fever, hand-foot syndrome, hyperglycemia, hypophosphatemia

Dacomitinib (Vizimpro)

45 mg orally once daily

Acute: diarrhea

Delayed: rash, paronychia, mucositis, cough, interstitial lung disease

Dasatinib (Sprycel)

100–180 mg orally once daily

Acute: diarrhea, nausea, vomiting

Delayed: myelosuppression, fluid retention, fatigue, dyspnea, musculoskeletal pain, rash

Entrectinib (Rozlytrek)

600 mg orally daily

Acute: nausea, vomiting, diarrhea

Delayed: fatigue, cognitive impairment, congestive heart failure, potential for birth defects, hepatotoxicity, vision disorder, prolonged QT interval (rare)

Erlotinib (Tarceva)

100 or 150 mg orally once daily without food

Acute: diarrhea, nausea, vomiting

Delayed: acneiform skin rash, fatigue, anorexia, dyspnea

Everolimus (Afinitor)

10 mg orally once daily

Acute: mucositis, diarrhea, nausea

Delayed: myelosuppression, fatigue, edema, hypercholesterolemia, hypertriglyceridemia, hyperglycemia

Gefitinib (Iressa)

250 mg orally once daily

Acute: diarrhea

Delayed: acneiform skin rash

Ibrutinib (Imbruvica)

420 or 560 mg orally once daily

Acute: diarrhea, nausea

Delayed: myelosuppression, fatigue, edema, rash, elevated serum creatinine, hemorrhage

Imatinib (Gleevec)

100–800 mg orally once daily with food

Acute: nausea, vomiting, diarrhea

Delayed: edema, muscle cramps, rash, myelosuppression, hepatotoxicity

Larotrectinib (Vitrakvi)

100 mg orally twice daily

Acute: nausea, vomiting, diarrhea

Delayed: fatigue, cognitive impairment, potential for birth defects, hepatotoxicity

Lenvatinib (Lenvima)

24 mg orally daily

Acute: hypertension, nausea, vomiting, diarrhea

Delayed: fatigue, arthralgia/myalgia, stomatitis, hand-foot syndrome

Nilotinib (Tasigna)

300 or 400 mg orally twice daily without food

Acute: nausea, vomiting, diarrhea

Delayed: rash, fatigue, myelosuppression, prolonged QT interval (rare)

Osimertinib (Tagrisso)

80 mg orally once daily

Acute: diarrhea

Delayed: myelosuppression, rash, dry skin, nail toxicity, cardiomyopathy (rare), QTc interval prolongation (rare)

Pazopanib (Votrient)

800 mg orally once daily without food

Acute: diarrhea, nausea, vomiting

Delayed: hypertension, hair color changes, hepatotoxicity, hemorrhage

Regorafenib (Stivarga)

160 mg orally once daily with food (low-fat breakfast)

Acute: diarrhea

Delayed: asthenia, hand-foot syndrome, anorexia, hypertension, mucositis, myelosuppression, hepatotoxicity

Sorafenib (Nexavar)

400 mg orally twice daily without food

Acute: diarrhea and nausea

Delayed: fatigue, hand-foot syndrome, rash, hypertension, hemorrhage

Sunitinib (Sutent)

50 mg orally once daily for 4 weeks followed by 2 weeks rest; 37.5 mg orally daily

Acute: diarrhea and nausea

Delayed: hypertension, hand-foot syndrome, rash, yellow discoloration of skin, fatigue, hypothyroidism, mucositis, left ventricular dysfunction, bleeding, hepatotoxicity

Trametinib (Mekinist)

2 mg orally once daily without food

Acute: rash, diarrhea

Delayed: elevated transaminases, lymphedema, cardiomyopathy

Vemurafenib (Zelboraf)

960 mg orally twice daily

Acute: nausea, hypersensitivity (rare)

Delayed: photosensitivity, rash, arthralgia, alopecia, fatigue, prolonged QT interval, cutaneous squamous cell carcinoma

Miscellaneous Agents

Abiraterone (Zytiga)

1000 mg orally once daily

Acute: diarrhea, edema

Delayed: adrenal insufficiency, hepatotoxicity, joint pain, hypokalemia

Arsenic trioxide (Trisenox)

0.15 mg/kg intravenously daily

Acute: nausea, dizziness

Delayed: acute promyelocytic leukemia differentiation syndrome, prolonged QT interval

Bleomycin (Blenoxane)

10 units/m² intravenously on days 1 and 15 every 28 days; 30 units intravenously on days 2, 9, and 16 every 21 days

Acute: hypersensitivity, fever

Delayed: skin reaction (rash, hyperpigmentation of skin, striae), mucositis, pneumonitis

Bortezomib (Velcade)

1.3 mg/m² intravenous bolus or subcutaneously on days 1, 4, 8, 11 followed by a 10-day rest, or weekly for 4 weeks followed by 13-day rest

Acute: nausea, vomiting, diarrhea

Delayed: peripheral neuropathy, fatigue, myelosuppression

Dactinomycin (Cosmegen)

15 mcg/kg or 400–600 mcg/m² intravenously daily for 5 days

Acute: nausea, vomiting

Delayed: myelosuppression, mucositis, rash, diarrhea, hepatoveno-occlusive disease (rare)

Hydroxyurea (Hydrea)

20–30 mg/kg orally daily

Acute: none

Delayed: myelosuppression

Lenalidomide (Revlimid)

5–25 mg orally once daily on days 1–21 of 28-day cycle; or continuously

Acute: diarrhea, rash

Delayed: myelosuppression, fatigue, venous thromboembolism, potential for birth defects

Mitomycin (Mutamycin)

10–20 mg/m² intravenously every 4–8 weeks; 20–40 mg intravesically

Acute: cystitis (intravesically), nausea, vomiting

Delayed: myelosuppression, mucositis, anorexia

Olaparib (Lynparza)

400 mg orally twice daily

Acute: nausea, vomiting, diarrhea

Delayed: myelosuppression, elevated serum creatinine, MCV elevation, fatigue, abdominal pain

Pegaspargase (Oncaspar)

2000–2500 international units/m² intramuscularly every 14 days

Acute: hypersensitivity

Delayed: febrile neutropenia, coagulation abnormalities, hepatotoxicity, pancreatitis

Tretinoin (All-Trans-Retinoic Acid, ATRA, Vesanoid)

45 mg/m² orally divided twice daily for 45–90 days or 30 days past complete remission

Acute: headache, nausea

Delayed: vitamin A toxicity, retinoic acid-acute promyelocytic leukemia syndrome

Venetoclax (Venclexta)

20 mg orally daily during week 1; 50 mg daily during week 2; 100 mg daily during week 3; 200 mg daily during week 4; then 400 mg orally daily thereafter

Acute: diarrhea, nausea, vomiting, tumor lysis syndrome

Delayed: myelosuppression, upper respiratory infections, fatigue

Antiandrogens

Apalutamide (Erleada)

240 mg orally daily

Acute: fatigue, diarrhea

Delayed: arthralgia, hot flashes, falls, peripheral edema, seizure (rare)

Bicalutamide (Casodex)

50 mg orally once daily

Acute: none

Delayed: hot flashes, back pain, asthenia

Enzalutamide (Xtandi)

160 mg orally once daily

Acute: asthenia, diarrhea

Delayed: hot flashes, arthralgia, peripheral edema, seizure (rare)

Flutamide (Eulexin)

250 mg orally every 8 hours

Acute: diarrhea

Delayed: hot flashes, hepatotoxicity

Nilutamide (Nilandron)

300 mg orally for 30 days, then 150 mg orally once daily

Acute: none

Delayed: visual disturbances (impaired adaptation to dark), hot flashes, disulfiram-like reaction

Selective Estrogen Receptor Modulators

Tamoxifen (Nolvadex)

20–40 mg orally once daily

Acute: none

Delayed: hot flashes, vaginal discharge, menstrual irregularities, arthralgia

Aromatase Inhibitors

Anastrozole (Arimidex)

1 mg orally once daily

Acute: nausea

Delayed: hot flashes, peripheral edema, asthenia, hypercholesterolemia, arthralgia/myalgia, osteoporosis

Exemestane (Aromasin)

25 mg orally once daily

Letrozole (Femara)

2.5 mg orally once daily

Pure Estrogen Receptor Antagonist

Fulvestrant (Faslodex)

500 mg intramuscularly on days 1, 15, 29, then monthly

Acute: injection site reaction, nausea

Delayed: hot flashes, bone pain, elevated transaminases

LHRH Analogs

Goserelin acetate (Zoladex)

3.6 mg subcutaneously every month; 10.8 mg subcutaneously every 3 months

Acute: injection site discomfort

Delayed: hot flashes, tumor flare, edema, decreased libido, erectile dysfunction, osteoporosis

Leuprolide (Lupron)

7.5 mg intramuscularly or subcutaneously every month; 22.5 mg intramuscularly or subcutaneously every 3 months; 30 mg intramuscularly or subcutaneously every 4 months; 45 mg intramuscularly or subcutaneously every 6 months

Triptorelin pamoate (Trelstar)

3.75 mg intramuscularly every 4 weeks; 11.25 mg intramuscularly every 12 weeks; 22.5 mg intramuscularly every 24 weeks

LHRH Antagonist

Degarelix (Firmagon)

240 mg subcutaneously once, then 80 mg subcutaneously every 28 days

Acute: injection site reaction

Delayed: hot flashes, weight gain, elevated transaminases, QT prolongation

AV, atrioventricular; GFR, glomerular filtration rate; LHRH, luteinizing hormone–releasing hormone; MAO, monoamine oxidase; MCV, mean corpuscular volume.

Table 39–13.Commonly used supportive care agents.¹

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Table 39–13. Commonly used supportive care agents.¹

Agent

Indication

Usual Dose

Adverse Effects

Allopurinol (Xyloprim)

Prevent hyperuricemia from tumor lysis syndrome

600–800 mg/day orally

Acute: none

Delayed: rash

Dexrazoxane (Zinecard)

Prevent cardiomyopathy secondary to doxorubicin; anthracycline-induced injection site extravasation

10 times the doxorubicin dose intravenously before doxorubicin; 1000 mg/m² intravenously on days 1 and 2, then 500 mg/m² intravenously on day 3

Acute: nausea

Delayed: myelosuppression, elevated transaminases

Leucovorin

Rescue after high-dose methotrexate; in combination with 5-fluorouracil for colon cancer

10 mg/m² intravenously or orally every 6 hours; 20 mg/m² or 200–500 mg/m² intravenously before 5-fluorouracil; various doses

Acute: nausea, vomiting, diarrhea

Delayed: stomatitis, fatigue

Levoleucovorin (Fusilev)

Rescue after high-dose methotrexate; in combination with 5-fluorouracil for colon cancer

7.5 mg intravenously every 6 hours for 10 doses; 100 mg/m² intravenously before 5-fluorouracil

Acute: nausea, vomiting

Delayed: stomatitis, diarrhea

Mesna (Mesnex)

Prevent ifosfamide-induced hemorrhagic cystitis

20% of ifosfamide dose intravenously at 0, 4, and 8 hours; various doses

Acute: nausea, vomiting

Delayed: fatigue

Palifermin (Kepivance)

Prevent mucositis following chemotherapy

60 mcg/kg/day intravenously for 3 days before and 3 days after chemotherapy

Acute: none

Delayed: rash, fever, elevated serum amylase, erythema, edema

Amifostine (Ethyol)

Prevent cisplatin nephropathy; prevent radiation-induced xerostomia

910 mg/m² intravenously before cisplatin; 200 mg/m² intravenously before radiation

Acute: nausea, vomiting, hypotension, infusion-related reaction

Delayed: hypocalcemia

Pilocarpine (Salagen)

Radiation-induced xerostomia

5–10 mg orally three times a day

Acute: flushing, sweating, nausea, dizziness

Delayed: increased urinary frequency, rhinitis

Radium (Ra)-223 dichloride (Xofigo)

Symptomatic bone metastases

50 kilobecquerel/kg (1.35 microCurie/kg) intravenously every 4 weeks for 6 cycles

Acute: nausea, vomiting, diarrhea, peripheral edema

Delayed: myelosuppression

Rasburicase (Elitek)

Prevent hyperuricemia from tumor lysis syndrome

3–6 mg intravenously once

Acute: hypersensitivity, nausea, vomiting, diarrhea, fever, headache

Delayed: rash, peripheral edema

Samarium (Sm)-153 (Quadramet)

Symptomatic bone metastasis

1 milliCurie/kg intravenously

Acute: pain flare

Delayed: myelosuppression

Strontium (Sr)-89 (Metastron)

Symptomatic bone metastasis

148 megabecquerels (4 milliCuries) intravenously; or 1.5–2.2 megabecquerels/kg (40–60 microCuries/kg)

Acute: bone pain

Delayed: myelosuppression

Bone-Modifying Agents

Denosumab (Xgeva)

Osteolytic bone metastasis

120 mg subcutaneously every 4 weeks

Acute: nausea

Delayed: hypocalcemia, hypophosphatemia, fatigue, osteonecrosis of the jaw

Pamidronate (Aredia)

Osteolytic bone metastasis, hypercalcemia of malignancy

90 mg intravenously every 3–4 weeks; 60–90 mg intravenously, may repeat after 7 days

Acute: nausea

Delayed: dyspnea, arthralgia, bone pain, osteonecrosis of the jaw, nephrotoxicity, hypocalcemia

Zoledronic acid (Zometa)

Osteolytic bone metastasis, hypercalcemia of malignancy

4 mg intravenously every 3–4 weeks; 4 mg intravenously once, may repeat after 7 days

—

Growth Factors

Darbepoetin alfa (Aranesp)

Chemotherapy-induced anemia

2.25 mcg/kg subcutaneously weekly; 500 mcg subcutaneously every 3 weeks

—

Epoetin alfa (Epogen, Procrit)

Chemotherapy-induced anemia

40,000 units subcutaneously once weekly; 150 units/kg subcutaneously three times a week

Acute: injection site reaction

Delayed: hypertension, thromboembolic events, increased risk of tumor progression or recurrence

Filgrastim (Neupogen)

Filgrastim-sndz (Zarxio)

Febrile neutropenia prophylaxis, mobilization of peripheral stem cells

5–10 mcg/kg/day subcutaneously or intravenously once daily, treat past nadir

Acute: injection site reaction

Delayed: bone pain

Pegfilgrastim (Neulasta)

Febrile neutropenia prophylaxis

6 mg subcutaneously once per chemotherapy cycle

—

Sargramostim (Leukine)

Myeloid reconstitution following bone marrow transplant, mobilization of peripheral blood stem cells

250 mcg/m² intravenously daily until the absolute neutrophil count is > 1500 cells/mcL for 3 consecutive days

Acute: fever, rash, pruritus, nausea, vomiting, diarrhea, injection site reaction, dyspnea

Delayed: asthenia, bone pain, mucositis, edema, arrhythmia

Tbo-filgrastim (Neutroval)

Severe chemotherapy-induced neutropenia

5 mcg/kg subcutaneously once daily until neutrophil recovery

Acute: none

Delayed: bone pain, leukocytosis

¹For amifostine, samarium, strontium, filgrastim-sndz, and tbo-filgrastim, see Table 39–13 in CMDT Online at www.accessmedicine.com.

Surgery

Most ovarian masses in postmenopausal women require surgical evaluation
However, a postmenopausal woman with an asymptomatic unilateral simple cyst ≤ 5 cm in diameter and a normal serum CA 125 level may be monitored closely with TVS. All others require surgical evaluation
Exploratory laparotomy has been the standard approach in postmenopausal women
For ovarian cancer in an early stage, the standard therapy is complete surgical staging followed by hysterectomy and bilateral salpingo-oophorectomy with omentectomy and selective lymphadenectomy
With more advanced disease, removal of all visible tumor improves survival
For benign neoplasms, tumor removal or unilateral oophorectomy is usually performed

Therapeutic Procedures

In a premenopausal woman, an asymptomatic, mobile, unilateral, simple cystic mass < 8–10 cm may be observed for 4–6 weeks
- Most will resolve spontaneously
- If the mass is larger or unchanged on repeat pelvic examination and TVS, surgical evaluation is required
Laparoscopy may be considered for a small ovarian mass in a premenopausal woman
If malignancy is suspected because of findings on transvaginal ultrasound with morphologic scoring, color Doppler assessment of vascular quality, and serum CA 125 level, then laparotomy is preferable

Outcome

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Prognosis

Approximately 75% of women with ovarian cancer are diagnosed with advanced disease after regional or distant metastases have become established
The overall 5-year survival is approximately 17% with distant metastases, 36% with local spread, and 89% with early disease

Prevention

Women with a BRCA1 gene mutation should be screened annually with TVS and serum CA 125 testing, and prophylactic oophorectomy is recommended by age 35 or whenever childbearing is no longer a consideration because of the high risk of disease
The benefits of such screening for women with one or no affected first-degree relatives are unproved, and the risks associated with unnecessary surgical procedures may outweigh the benefits in low-risk women

When to Refer

If a malignant ovarian mass is suspected, surgical evaluation should be performed by a gynecologic oncologist

References

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American College of Obstetricians and Gynecologists. Committee Opinion No. 716: The role of the obstetrician-gynecologist in the early detection of epithelial ovarian cancer in women at average risk. Obstet Gynecol. 2017 Sep;130(3):e146–9.
[PubMed: 28832487]

American College of Obstetricians and Gynecologists. ACOG Committee Opinion No. 793: Hereditary cancer syndromes and risk assessment. Obstet Gynecol. 2019 Dec;134(6):e143–9.
[PubMed: 31764758]

Centers for Disease Control and Prevention (CDC). Ovarian cancer screening. 2019 Aug 15. https://www.cdc.gov/cancer/ovarian/basic_info/screening.htm

US Preventive Services Task Force, Grossman DC et al. Screening for ovarian cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Feb 13;319(6):588–94.
[PubMed: 29450531]

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Ovarian Cancer & Other Tumors

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Key Features

Essentials of Diagnosis

General Considerations

Demographics

Clinical Findings

Symptoms and Signs

Differential Diagnosis

Diagnosis

Laboratory Tests

Imaging Studies

Treatment

Medications

Surgery

Therapeutic Procedures

Outcome

Prognosis

Prevention

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References

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