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
  • 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: 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

• 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) 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 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 are:
    • Carboplatin/Paclitaxel
    • Carboplatin/Paclitaxel/Bevacizumab
    • Carboplatin/Gemcitabine
    • Carboplatin/Gemcitabine/Bevacizumab
    • Carboplatin/liposomal Doxorubicin with or without Bevacizumab
    • Cisplatin/Gemcitabine

• Non-platinum-based agents if platinum-resistant
  
  • Preferred agents are:
    • 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
  • Can be used as maintenance therapy in patients who were responsive until disease progression or unacceptable toxicity; data on Bevacizumab efficacy as recurrence therapy is limited in patients who had previously received it
• 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, Altretamine, Capecitabine, Doxorubicin, Melphalan, Oxaliplatin, Paclitaxel, albumin-bound Paclitaxel, Pemetrexed, Sorafenib/Topotecan, Vinorelbine, Pazopanib, Carboplatin/Paclitaxel weekly combination for platinum-sensitive disease, hormonal therapy (eg Megestrol acetate, aromatase inhibitors, Leuprolide acetate, Tamoxifen)
• 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
  • Microsatellite instability-high [MSI-H] or mismatch, repair-deficient [dMMR] solid tumors: Pembrolizumab

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