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OVARIAN CANCER
TUMOR MARKERS
BRCA1 and BRCA2 gene mutations
Cancer types: Ovarian and breast cancers
What's analyzed: Blood and/or tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate
CA-125
Cancer type: Ovarian cancer
What's analyzed: Blood
How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence
The normal value is less than 46 U/mL. If your CA 125 level is higher than normal, you may have a benign
condition, or the test result could mean that you have ovarian, endometrial, peritoneal or fallopian tube
cancer
HE4
Cancer type: Ovarian cancer
What's analyzed: Blood
How used: To plan cancer treatment, assess disease progression, and monitor for recurrence
The normal range of circulating HE4 is ≤150 picomoles/L, or picomolar (pM). In one study, the mean
serum HE4 level in healthy control women was 41 pM; in those who had ovarian cancer, 1,125 pM
HER2/neu gene amplification or protein overexpression
Cancer types: Breast, ovarian, bladder, pancreatic, and stomach cancers
What's analyzed: Tumor
How used: To determine whether treatment with certain targeted therapies is appropriate
Protein signature (OVA1®)
Cancer type: Ovarian cancer
What's analyzed: Blood
How used: To pre-operatively assess pelvic mass for suspected ovarian cancer
TREATMENT CONSIDERATIONS:-
For women who have stage III ovarian cancer (cancer that has not spread outside the abdomen) and
whose cancers were optimally debulked (no tumors larger than 1 cm after surgery), intraperitoneal (IP)
chemotherapy might be given in addition to systemic chemo (paclitaxel given in a vein).
In IP chemotherapy, the drugs cisplatin and paclitaxel are injected into the abdominal cavity through a
catheter (thin tube).
Paclitaxel 135 mg/m2 continuous IV infusion over 3 h or 24 h on day 1 plus cisplatin 75-100 mg/m2 IP on
day 2 (may reduce dose to 75 mg/m2) plus paclitaxel 60 mg/m2 IP on day 8; repeat every 3 weeks for si6
cycles, provided that the disease is responsive [10]
If the patient cannot tolerate IP delivery, revert to one of the following two drug regimens:
Paclitaxel 175 mg/m2 IV over 3 h plus carboplatin AUC 5-6 IV over 1 h on day 1; every 21 d for six cycles
[13
Stage IVA:
Treatment recommendations are similar to those for stage III.
Stage IVB:
Patients should be considered for front-line chemotherapy and should strongly consider participation in
clinical trials if the option is available. Possible regimens are as follows:
Paclitaxel 175 mg/m2 IV over 3 h plus carboplatin AUC 5-6 IV over 1 h on day 1; every 21 d for six cycles
[13] or
Docetaxel 75 mg/m2 IV over 1 h plus carboplatin AUC 5 IV over 1 h on day 1; every 21 d for six cycles [8]
Chemotherapy recommendations for recurrent disease
Stages III and IV disease have a high rate of recurrence. These patients should be considered for clinical
trials. Treatment is usually with chemotherapy; the regimen choice depends on the time elapsed since
previous complete response to platinum-containing chemotherapy.
Platinum-sensitive recurrence:
Bevacizumab 7.5 mg/kg IV over 30-90 min on Day 1 plus carboplatin AUC 5-6 IV on day 1 plus paclitaxel
175 mg/m2 IV over 3 h on day 1 every 21 days for five to six cycles, followed by continued use of
bevacizumab 7.5 mg/kg every 21 days for up to 12 additional cycles.
Platinum-resistant recurrence:
If recurrence occurs less than 6 months after initial or subsequent complete clinical response to
platinum-containing chemotherapy, the patient should be treated with one of the regimens below.
There is no standard for the number of cycles of treatment given in this situation. Often treatment is
changed because of progressive disease or toxicity.
Although liposomal doxorubicin is a good first choice, many other agents with similar efficacy are
available; the final choice depends on individual circumstance and patient and physician preference.
Some of the choices include the following:
Liposomal doxorubicin 40-50 mg/m2 IV over 30 min; every 21 d [31, 32, 33] or
Gemcitabine 1000 mg/m² IV over 30 min on Days 1 and 8; every 21 d [32, 33, 34] or
PARP inhibitors are FDA approved as maintenance or treatment in a platinum-sensitive relapse in
patients who have had at least a partial platinum response.
Olaparib treatment indication
Deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer in
patients who have been treated with three or more prior lines of chemotherapy
Capsules: 400 mg PO BID [46]
Tablets: 300 mg (tablet) PO BID [47, 48]
Olaparib maintenance indications
Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, in patients who have in
complete or partial response to platinum-based chemotherapy
First-line maintenance treatment of deleterious or suspected deleterious germline or somatic BRCA-
mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal
cancer in patients who are in complete or partial response to first-line platinum based chemotherapy
Tablets only: 300 mg PO BID
Rucaparib (Rubraca) 600 mg PO BID continuously is indicated for monotherapy of women with
deleterious BRCA mutations (germline and/or somatic) associated with advanced ovarian cancer who
have been treated with two or more prior lines of chemotherapy. [49] This agent is also indicated for
maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in
patients who are in a complete or partial response to platinum-based chemotherapy. [50, 49]
Niraparib (Zejula) 300 mg PO daily is approved for maintenance treatment for recurrent epithelial
ovarian, fallopian tube, or primary peritoneal cancer in women who have had complete or partial
response to platinum-based chemotherapy independent of BRCA status. [51].
Hormonal therapy
Hormonal therapy may be considered for patients who have asymptomatic recurrence or who require a
break from regular chemotherapy if they are not tolerating treatment well, as follows:
Tamoxifen [52, 53, 54] 20 mg PO twice a day daily or
Letrozole [55] 2.5 mg PO daily
Elderly patients may not tolerate chemotherapy as well as younger patients.
Carboplatin AUC 5 IV plus paclitaxel 135 mg/m2; every 21 d [56] or
Chemotherapy for epithelial ovarian cancer
Chemo for ovarian cancer usually involves getting two different types of drugs together. Getting a
combination of drugs instead of just one drug alone seems to work better as a first treatment for
ovarian cancer. Usually, the combination includes a type of chemo drug called a platinum compound
(usually cisplatin or carboplatin), and another type of chemo drug called a taxane, such as paclitaxel
(Taxol®) or docetaxel (Taxotere®). These drugs are usually given as an IV (put into a vein) every 3 to 4
weeks.
Chemotherapy for germ cell tumors
If you have a germ cell tumor, you will likely be treated with combination chemo (several different drugs
at once). The combination used most often is called BEP
Bleomycin 30 units fixed dose IV on days 2, 9, and 16.
Etoposide 100mg/m2 IV on days 1, 2, 3, 4, and 5.
Cisplatin 20mg/m2 IV on days 1, 2, 3, 4, and 5.
, and includes the chemotherapy drugs bleomycin, etoposide and cisplatin (Platinol). If the cancer is a
dysgerminoma, these are usually very sensitive to chemotherapy, and can sometimes be treated with
the less toxic combination of carboplatin and etoposide. Other drug combinations may be used if the
cancer isn’t responding to treatment or to treat cancer that has recurred (come back). These include:
High dose chemotherapy (the exact drugs used can vary depending on what cancer center is giving the
treatment)
TIP (paclitaxel/Taxol, ifosfamide, and cisplatin/Platinol)
VeIP (vinblastine, ifosfamide, and cisplatin/Platinol)
VIP (etoposide/VP-16, ifosfamide, and cisplatin/Platinol)
Etoposide 75mg/m2 on days 1, 2, 3, 4, 5.
Mesna 400mg/m2 every four hours X three doses on days 1, 2, 3, 4, 5(total daily dose of mesna =
1200mg/m2).
Ifosfamide 1200mg/m2 on days 1, 2, 3, 4, 5.
Cisplatin 20mg/m2 on days 1, 2, 3, 4, 5.
Cycle length 21 days.
VAC (vincristine, dactinomycin, and cyclophosphamide)
Chemotherapy for stromal tumors
Ovarian stromal tumors are not often treated with chemotherapy, but when they are, the combination
of carboplatin plus paclitaxel or PEB (cisplatin/Platinol, etoposide, and bleomycin) is used most often.

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Ovarian cancer regimens

  • 1. OVARIAN CANCER TUMOR MARKERS BRCA1 and BRCA2 gene mutations Cancer types: Ovarian and breast cancers What's analyzed: Blood and/or tumor How used: To determine whether treatment with a particular type of targeted therapy is appropriate CA-125 Cancer type: Ovarian cancer What's analyzed: Blood How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence The normal value is less than 46 U/mL. If your CA 125 level is higher than normal, you may have a benign condition, or the test result could mean that you have ovarian, endometrial, peritoneal or fallopian tube cancer HE4 Cancer type: Ovarian cancer What's analyzed: Blood How used: To plan cancer treatment, assess disease progression, and monitor for recurrence The normal range of circulating HE4 is ≤150 picomoles/L, or picomolar (pM). In one study, the mean serum HE4 level in healthy control women was 41 pM; in those who had ovarian cancer, 1,125 pM HER2/neu gene amplification or protein overexpression Cancer types: Breast, ovarian, bladder, pancreatic, and stomach cancers What's analyzed: Tumor How used: To determine whether treatment with certain targeted therapies is appropriate Protein signature (OVA1®) Cancer type: Ovarian cancer What's analyzed: Blood
  • 2. How used: To pre-operatively assess pelvic mass for suspected ovarian cancer TREATMENT CONSIDERATIONS:- For women who have stage III ovarian cancer (cancer that has not spread outside the abdomen) and whose cancers were optimally debulked (no tumors larger than 1 cm after surgery), intraperitoneal (IP) chemotherapy might be given in addition to systemic chemo (paclitaxel given in a vein). In IP chemotherapy, the drugs cisplatin and paclitaxel are injected into the abdominal cavity through a catheter (thin tube). Paclitaxel 135 mg/m2 continuous IV infusion over 3 h or 24 h on day 1 plus cisplatin 75-100 mg/m2 IP on day 2 (may reduce dose to 75 mg/m2) plus paclitaxel 60 mg/m2 IP on day 8; repeat every 3 weeks for si6 cycles, provided that the disease is responsive [10] If the patient cannot tolerate IP delivery, revert to one of the following two drug regimens: Paclitaxel 175 mg/m2 IV over 3 h plus carboplatin AUC 5-6 IV over 1 h on day 1; every 21 d for six cycles [13 Stage IVA: Treatment recommendations are similar to those for stage III. Stage IVB: Patients should be considered for front-line chemotherapy and should strongly consider participation in clinical trials if the option is available. Possible regimens are as follows: Paclitaxel 175 mg/m2 IV over 3 h plus carboplatin AUC 5-6 IV over 1 h on day 1; every 21 d for six cycles [13] or Docetaxel 75 mg/m2 IV over 1 h plus carboplatin AUC 5 IV over 1 h on day 1; every 21 d for six cycles [8] Chemotherapy recommendations for recurrent disease Stages III and IV disease have a high rate of recurrence. These patients should be considered for clinical trials. Treatment is usually with chemotherapy; the regimen choice depends on the time elapsed since previous complete response to platinum-containing chemotherapy. Platinum-sensitive recurrence: Bevacizumab 7.5 mg/kg IV over 30-90 min on Day 1 plus carboplatin AUC 5-6 IV on day 1 plus paclitaxel 175 mg/m2 IV over 3 h on day 1 every 21 days for five to six cycles, followed by continued use of bevacizumab 7.5 mg/kg every 21 days for up to 12 additional cycles. Platinum-resistant recurrence:
  • 3. If recurrence occurs less than 6 months after initial or subsequent complete clinical response to platinum-containing chemotherapy, the patient should be treated with one of the regimens below. There is no standard for the number of cycles of treatment given in this situation. Often treatment is changed because of progressive disease or toxicity. Although liposomal doxorubicin is a good first choice, many other agents with similar efficacy are available; the final choice depends on individual circumstance and patient and physician preference. Some of the choices include the following: Liposomal doxorubicin 40-50 mg/m2 IV over 30 min; every 21 d [31, 32, 33] or Gemcitabine 1000 mg/m² IV over 30 min on Days 1 and 8; every 21 d [32, 33, 34] or PARP inhibitors are FDA approved as maintenance or treatment in a platinum-sensitive relapse in patients who have had at least a partial platinum response. Olaparib treatment indication Deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer in patients who have been treated with three or more prior lines of chemotherapy Capsules: 400 mg PO BID [46] Tablets: 300 mg (tablet) PO BID [47, 48] Olaparib maintenance indications Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, in patients who have in complete or partial response to platinum-based chemotherapy First-line maintenance treatment of deleterious or suspected deleterious germline or somatic BRCA- mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to first-line platinum based chemotherapy Tablets only: 300 mg PO BID Rucaparib (Rubraca) 600 mg PO BID continuously is indicated for monotherapy of women with deleterious BRCA mutations (germline and/or somatic) associated with advanced ovarian cancer who have been treated with two or more prior lines of chemotherapy. [49] This agent is also indicated for maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in a complete or partial response to platinum-based chemotherapy. [50, 49] Niraparib (Zejula) 300 mg PO daily is approved for maintenance treatment for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in women who have had complete or partial response to platinum-based chemotherapy independent of BRCA status. [51]. Hormonal therapy
  • 4. Hormonal therapy may be considered for patients who have asymptomatic recurrence or who require a break from regular chemotherapy if they are not tolerating treatment well, as follows: Tamoxifen [52, 53, 54] 20 mg PO twice a day daily or Letrozole [55] 2.5 mg PO daily Elderly patients may not tolerate chemotherapy as well as younger patients. Carboplatin AUC 5 IV plus paclitaxel 135 mg/m2; every 21 d [56] or Chemotherapy for epithelial ovarian cancer Chemo for ovarian cancer usually involves getting two different types of drugs together. Getting a combination of drugs instead of just one drug alone seems to work better as a first treatment for ovarian cancer. Usually, the combination includes a type of chemo drug called a platinum compound (usually cisplatin or carboplatin), and another type of chemo drug called a taxane, such as paclitaxel (Taxol®) or docetaxel (Taxotere®). These drugs are usually given as an IV (put into a vein) every 3 to 4 weeks. Chemotherapy for germ cell tumors If you have a germ cell tumor, you will likely be treated with combination chemo (several different drugs at once). The combination used most often is called BEP Bleomycin 30 units fixed dose IV on days 2, 9, and 16. Etoposide 100mg/m2 IV on days 1, 2, 3, 4, and 5. Cisplatin 20mg/m2 IV on days 1, 2, 3, 4, and 5. , and includes the chemotherapy drugs bleomycin, etoposide and cisplatin (Platinol). If the cancer is a dysgerminoma, these are usually very sensitive to chemotherapy, and can sometimes be treated with the less toxic combination of carboplatin and etoposide. Other drug combinations may be used if the cancer isn’t responding to treatment or to treat cancer that has recurred (come back). These include: High dose chemotherapy (the exact drugs used can vary depending on what cancer center is giving the treatment) TIP (paclitaxel/Taxol, ifosfamide, and cisplatin/Platinol) VeIP (vinblastine, ifosfamide, and cisplatin/Platinol) VIP (etoposide/VP-16, ifosfamide, and cisplatin/Platinol) Etoposide 75mg/m2 on days 1, 2, 3, 4, 5. Mesna 400mg/m2 every four hours X three doses on days 1, 2, 3, 4, 5(total daily dose of mesna = 1200mg/m2). Ifosfamide 1200mg/m2 on days 1, 2, 3, 4, 5.
  • 5. Cisplatin 20mg/m2 on days 1, 2, 3, 4, 5. Cycle length 21 days. VAC (vincristine, dactinomycin, and cyclophosphamide) Chemotherapy for stromal tumors Ovarian stromal tumors are not often treated with chemotherapy, but when they are, the combination of carboplatin plus paclitaxel or PEB (cisplatin/Platinol, etoposide, and bleomycin) is used most often.