ovarian%20cancer
OVARIAN CANCER
Ovarian cancer is a type of cancer that begins in the ovaries.
It is the 7th most common cancer in women (excluding skin cancer) and the leading cause of death from gynecologic cancer in developed countries.
The 3 histologic types of ovarian cancer are epithelial (primarily seen in women >50 years of age), germ cell (most commonly seen in women <20 years of age) and sex cord stromal (rare and produces steroid hormones).
The median age at the time of diagnosis is 63 years old and >70% present with advanced disease.

    Ovarian%20cancer Treatment

    Pharmacotherapy

    Neoadjuvant Chemotherapy for Epithelial Ovarian Carcinoma

    • Should be considered in patients with advanced-stage ovarian cancer who are not good candidates for upfront primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have disease unlikely to be optimally cytoreduced
    • Recommended neoadjuvant chemotherapy regimens include Paclitaxel/carboplatin, dose-dense Paclitaxel/Carboplatin, Docetaxel/Carboplatin, Carboplatin/pegylated liposomal Doxorubicin and Paclitaxel/Carboplatin/Bevacizumab
      • Regimens that include Bevacizumab should be used with caution before IDS due to its effect on postoperative healing
    • Hyperthermic intraperitoneal chemotherapy (HIPEC) may be considered in patients with stage III disease being given neoadjuvant therapy at the time of IDS

    Chemotherapy for Epithelial Ovarian Carcinoma

    • Most patients receive postoperative systemic chemotherapy
    • After surgical cytoreduction, platinum-based chemotherapy is the treatment of choice for patients with advanced epithelial ovarian cancer
      • Monotherapy with Carboplatin every 3 weeks for 6 cycles as adjuvant therapy can be given in early-stage epithelial ovarian cancer; Cisplatin may be an alternative to Carboplatin
    • Recommendations for the number of cycles of treatment vary with the stage of the disease
      • Earlier stage disease: 3-6 cycles; advanced stages (II-IV): 6 cycles

    Recommended Primary Chemotherapy Regimens for Stage I Disease

    • Preferred regimens:
      • Paclitaxel/Carboplatin
      • 5-FU/Leucovorin/Oxaliplatin: Mucinous carcinoma stage IC
      • Capecitabine/Oxaliplatin: Mucinous carcinoma stage IC
    • Other recommended regimens:
      • Carboplatin/liposomal Doxorubicin
      • Docetaxel/Carboplatin
      • Hormone therapy (Eg Anastrozole, Letrozole, Exemestane, Leuprolide acetate, Tamoxifen): Low-grade serous (stage IC) or grade I endometrioid (stage IC)
    • Conditional regimens:
      • Carboplatin monotherapy: For patients >70 years of age and/or with comorbidities
      • Carboplatin or Cisplatin or Paclitaxel plus Ifosfamide: For carcinosarcoma

    Recommended Primary Chemotherapy Regimens for Stage II-IV Disease

    • Preferred regimens:
      • Paclitaxel/Carboplatin
      • Paclitaxel/Carboplatin/Bevacizumab plus maintenance Bevacizumab
        • A Bevacizumab biosimilar (eg Bevacizumab-awwb, Bevacizumab-bvzr) may be used in place of Bevacizumab
      • 5-FU/Leucovorin/Oxaliplatin with or without Bevacizumab: Mucinous carcinoma
      • Capecitabine/Oxaliplatin with or without Bevacizumab: Mucinous carcinoma
    • Other recommended regimens:
      • Weekly Paclitaxel/weekly Carboplatin
      • Docetaxel/Carboplatin
      • Carboplatin/liposomal Doxorubicin
      • Weekly Paclitaxel/3-weekly Carboplatin
      • Hormone therapy (Eg Anastrozole, Letrozole, Exemestane, Leuprolide acetate, Tamoxifen): Low-grade serous or grade I endometrioid
    • Conditional regimens:
      • Intraperitoneal (IP) or IV Paclitaxel/Cisplatin: For optimally-debulked stage II-III disease
      • Carboplatin or Cisplatin or Paclitaxel plus Ifosfamide: For carcinosarcoma
      • Carboplatin monotherapy: For patients >70 years of age and/or with comorbidities

    Recommended IV Regimens

    • Have different toxicity profiles
      • Paclitaxel followed by Carboplatin given every 3 weeks for 3-6 cycles
      • Paclitaxel followed by Carboplatin weekly for 18 weeks
      • Docetaxel followed by Carboplatin given every 3 weeks for 3-6 cycles
      • Dose-dense Paclitaxel on days 1, 8 and 15 plus Carboplatin on day 1 every 3 weeks for 6 cycles
      • Carboplatin plus pegylated liposomal Doxorubicin every 4 weeks for 3-6 cycles
      • Paclitaxel followed by Carboplatin and Bevacizumab every 3 weeks for 5-6 cycles
        • Continue Bevacizumab for up to 12 additional cycles
      • Paclitaxel followed by Carboplatin every 3 weeks for 6 cycles; add Bevacizumab starting cycle 2
        • Continue Bevacizumab up to 22 cycles

    Intraperitoneal (IP) Chemotherapy

    • Allows the possibility of targeting therapy to the site of disease while minimizing systemic toxicities
    • Recommended for all stage III patients with optimally debulked (<1 cm residual) disease
    • Stage II patients may also receive IP chemotherapy
    • Recommended regimen: Cisplatin on day 2 after IV Paclitaxel on day 1, then Paclitaxel on day 8, every 3 weeks for 6 cycles
    • IP Carboplatin given with IV Paclitaxel on day 1, followed by IP Paclitaxel on day 8 is a treatment option for patients who received neoadjuvant chemotherapy and interval debulking surgery
    • Women unable to complete IP therapy should receive IV therapy
    • Catheter complications, nausea, vomiting, dehydration, or abdominal pain are common reasons for discontinuing the IP treatment
    Borderline Epithelial Ovarian Carcinoma
    • Additional chemotherapeutic option is hormone therapy including aromatase inhibitors (Anastrozole, Letrozole), Leuprolide and Tamoxifen

    Chemotherapy for Germ Cell Ovarian Carcinoma

    • Patients with embryonal or endodermal sinus tumors, stage II-IV dysgerminoma or stage I, grade 2-3 or stage II-IV immature teratoma should receive postoperative chemotherapy with Bleomycin/Etoposide/Cisplatin for 3-4 cycles
    • In some patients with stage IB-III dysgerminoma for whom minimizing toxicity is critical, 3 courses of Etoposide/Carboplatin combination can be used: Carboplatin on day 1 plus Etoposide on days 1-3 every 4 weeks for 3 cycles

    Chemotherapy for Sex Cord Stromal Ovarian Carcinoma

    • For patients with stage II-IV tumors, platinum-based chemotherapy (Bleomycin/Etoposide/Cisplatin or Paclitaxel/Carboplatin, Etoposide/Cisplatin) regimens are preferred
    • Platinum-based chemotherapy should be considered for patients with high-risk stage 1 tumors
    • Patients with limited stage II-IV tumors should undergo radiotherapy

    Recurrence Therapy

    Recurrence Therapy for Epithelial Ovarian Carcinoma

    Cytotoxic Therapy

    • Combination platinum-based chemotherapy
      • Preferred for first recurrence in platinum-sensitive patients (ie patients who relapse ≥6 months after initial chemotherapy)
      • The decision regarding which combination to use should be based on the toxicity experienced with primary therapy, patient preference and other factors
      • Preferred agents for platinum-sensitive disease include:
        • Carboplatin/Paclitaxel with or without Bevacizumab
        • Carboplatin/Gemcitabine with or without Bevacizumab
        • Carboplatin/liposomal Doxorubicin with or without Bevacizumab
        • Cisplatin/Gemcitabine
    • Preferred non-platinum-based agents for platinum-resistant disease include:
      • Docetaxel
      • Oral Etoposide
      • Gemcitabine
      • Liposomal Doxorubicin
      • Weekly Paclitaxel
      • Topotecan
      • Topotecan/Bevacizumab
      • Weekly Paclitaxel/Bevacizumab
      • Liposomal Doxorubicin/Bevacizumab
      • Oral Cyclophosphamide/Bevacizumab

    Targeted Therapy

    • Bevacizumab is the preferred agent which was shown to slow down the growth of advanced ovarian cancer
      • Recommended for patients with platinum-resistant recurrent disease with history of ≤2 prior chemotherapy regimens, to be given in combination with Paclitaxel, pegylated liposomal Doxorubicin or Topotecan
      • May be used as maintenance therapy in patients with stage II-IV disease with wild-type or unknown BRCA1/2 mutation who were responsive until disease progression or unacceptable toxicity
    • Olaparib/Bevacizumab combination maintenance therapy may be considered in patients with BRCA1/2 mutations or genomic instability previously given Bevacizumab-containing platinum-based chemotherapy 
    • Olaparib may be given to patients with advanced ovarian cancer with germline BRCA mutation with complete orpartial response after ≥2 lines of chemotherapy
    • Niraparib may be given to patients with homologous recombination deficient (HRD)-positive advanced ovarian cancer for those who have undergone treatment with ≥3 lines of chemotherapy 
    • Rucaparib (platinum-resistant disease) may be given to patients with advanced ovarian cancer with germline and/or somatic BRCA mutation who have undergone treatment with ≥2 lines of chemotherapy 
    • Poly(ADP-ribose) polymerase (PARP) inhibitors Olaparib, Niraparib and Rucaparib are maintenance therapy options for patients with recurrent disease with complete or partial response to platinum-based chemotherapy
      • Niraparib maintenance therapy is an option for patients with wild-type or unknown BRCA1/2 mutation

    Other Agents 

    • Other therapeutic agents for recurrence include Altretamine, Capecitabine, Cyclophosphamide, Doxorubicin, hormonal therapy (eg aromatase inhibitors, Leuprolide acetate, Megestrol acetate, Tamoxifen), Ifosfamide, Irinotecan, Melphalan, Oxaliplatin, Paclitaxel, albumin-bound Paclitaxel, Pazopanib, Pemetrexed, Sorafenib/Topotecan, Vinorelbine
      • Carboplatin, Carboplatin/Docetaxel, Carboplatin/Paclitaxel weekly combination, Cisplatin, Nirapanib/Bevacizumab may also be used for platinum-sensitive disease
      • Pazopanib may be considered for patients with disease recurrence who had complete response to initial therapy
    • Other agents to be considered in certain circumstances:
      • Mucinous carcinoma: 5-FU/Leucovorin/Oxaliplatin with or without Bevacizumab & Capecitabine/Oxaliplatin with or without Bevacizumab
      • Clear cell carcinoma: Irinotecan/Cisplatin
      • NTRK gene fusion-positive carcinoma: Entrectinib, Larotrectinib
      • Confirmed taxane hypersensitivity: Carboplatin/albumin-bound Paclitaxel
      • Low-grade serous carcinoma: Fulvestrant, Trametinib
      • Microsatellite instability-high [MSI-H] or mismatch, repair-deficient [dMMR] solid tumors: Pembrolizumab
      • For patients >70 years of age: Carboplatin/Paclitaxel

    Recurrence Therapy for Germ Cell Ovarian Carcinoma

    • Recommended in patients with recurrent or residual disease after multiple chemotherapeutic regimens for whom no curative options are considered possible
    • Options may include Paclitaxel/Ifosfamide/Cisplatin (TIP), Vincristine/Dactinomycin/Cyclophosphamide (VAC), Vinblastine/Ifosfamide/Cisplatin (VeIP), Etoposide/Ifosfamide/Cisplatin (VIP), Cisplatin/Etoposide, Docetaxel/Carboplatin, Paclitaxel/Carboplatin, Paclitaxel/Gemcitabine, Paclitaxel/Ifosfamide, Docetaxel, Paclitaxel, high-dose chemotherapy, radiation therapy, or supportive care
      • Combination chemotherapy is not recommended in patients with recurrent or residual disease who have no curative options
      • Ifosfamide/platinum-based chemotherapy with or without Paclitaxel should be considered as 2nd-line option for patients with platinum-sensitive relapsed disease whose progression occurred >4-6 weeks after completion of primary therapy

    Recurrence Therapy for Sex Cord-Stromal Ovarian Carcinoma

    • Acceptable chemotherapy regimens include Bevacizumab, Bleomycin/Etoposide/Cisplatin, Docetaxel, Etoposide/Cisplatin, Paclitaxel, Paclitaxel/Carboplatin, Paclitaxel/Ifosfamide, Tamoxifen, VAC, aromatase inhibitors, radiation therapy, or supportive care
      • Leuprolide may be used for granulosa cell tumors
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