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.

    Pharmacotherapy

    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
    • Observation is recommended in patients with stage IA or IB, grade 1 tumors
      • Survival is >90% with surgical treatment alone
    • 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 IV Regimens

    • Have different toxicity profiles
      • Paclitaxel followed by Carboplatin given every 3 weeks for 6 cycles
      • Paclitaxel followed by Carboplatin weekly for 18 weeks
      • Docetaxel followed by Carboplatin given every 3 weeks for 6 cycles
      • Dose-dense Paclitaxel on days 1, 8 and 15 plus Carboplatin on day 1 every 3 weeks for 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: Paclitaxel on day 1 and 8; Cisplatin on day 2 every 3 weeks for 6 cycles
    • 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/platinum for 3-4 cycles
    • In some patients with stage IB-III dysgerminoma for whom minimizing toxicity is critical, 3 courses of Etoposide/Carboplatin can be used 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/Paclitaxel or Paclitaxel/Carboplatin) 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 are Carboplatin/Paclitaxel, Carboplatin/weekly Paclitaxel, Carboplatin/Docetaxel, Carboplatin/Gemcitabine, Carboplatin/Gemcitabine/Bevacizumab, Carboplatin/liposomal Doxorubicin, Cisplatin/Gemcitabine, and liposomal Doxorubicin/Trabectedin
    • Single agent if platinum-sensitive
      • Should be considered if combination platinum-based chemotherapy is contraindicated
      • Preferred agents are Carboplatin and Cisplatin
        • Carboplatin has shown manageable toxicity profile 
    • Non-platinum-based agents if platinum-resistant
      • Preferred agents are Docetaxel, oral Etoposide, Gemcitabine, liposomal Doxorubicin, weekly Paclitaxel with or without Pazoparib, Topotecan, Topotecan/Bevacizumab, weekly Paclitaxel/Bevacizumab, liposomal Doxorubicin/Bevacizumab

    Targeted Therapy

    • Bevacizumab is the preferred agent which was shown to slow down the growth of advanced ovarian CA
    • Olaparib may be given to patients with advanced ovarian cancer with germline BRCA mutation who have undergone treatment with ≥3 lines of chemotherapy with at least 2 courses of platinum-based regimens in previous treatment
    • 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 

    Other Agents 

    • Other therapeutic agents for recurrence include Cyclophosphamide, Ifosfamide, Irinotecan, Carboplatin/Paclitaxel/Bevacizumab combination for platinum-sensitive disease, hormonal therapy (eg Megestrol acetate, aromatase inhibitors, Leuprolide acetate, Tamoxifen)

    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

    Recurrence Therapy for Sex Cord Stromal Ovarian Carcinoma

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