Recurrent Ovarian Cancer

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Recurrent Ovarian Cancer
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Summary of Randomized Single Agent Trials
Recurrent Ovarian Cancer
Drug A Topotecan Paclitaxel (bolus) Oxalipla
tin Doxil Doxil Topotecan
Drug B Paclitaxel Paclitaxel
(weekly) Paclitaxel Topotecan Paclitaxel T
reosulfan
TTP (wks) 23 vs. 14 38 vs. 26 12 vs. 14 16
vs 17 22 vs. 22 22 vs. 12
OS (wks) 61 vs. 43 64 vs. 59 42 vs. 37 60
vs 57 46 vs. 56 56 vs. 48
P NS NS NS NS NS 0.02
P NS NS NS NS NS 0.001
Comment Cross-over confirmed in 50 Less
toxicity (wkly), no diff HSR 74 of cohort
Plat-resistant 54 Plat-resist Doxil OS
benefit in plat-sensitive subgroup All patients
taxane-naïve 2nd and 3rd line, Topo more Myelo
N 226 208 86 481 214 357
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Chemotherapy for Germ Cell Cancers of the Ovary
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Cervical Cancer
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Expected Response by Stage to Chemotherapy for
Cervical Cancer
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Chemotherapy Treatment for Cervical Cancer
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Vulvar Cancer
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Concurrent Chemotherapy and Radiation for Vulvar
Cancer

• 5-FU CDDP
• 5-FU Mitomycin C
• Bleomycin

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Common Complications of Chemotherapy and
Management

• Neutropenia
• Thrombocytopenia
• Mucocitis
• Palmar Plantar Erythrodesia
• Nausea / Vomitting
• Lethargy
• Hypersensitivity

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Cardiac toxicity

• Cylophosphamide (in high doses) acute cardiac
  necrosis
• Doxorubicin (cardiomyopathy, usually years after
  treatment due to loss of myofibrils but also
  cause acute myocarditis and pericarditis) acute
  and chronic
• Mitoxantrone
• busulfan (endocardial fibrosis)
• Mitomycin C (myocardial fibrosis) cardiomyopathy
• Taxol arrhythmias
• 5-FU myocardial ischemia (rare

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Pulmonary Toxicity

• Bleomycin-pulmonary fibrosis, pneumonitis,
  perioperative respiratory failure
• Cyclophosphamide (rare) Bislfan lung
• Dactinomycin if XRT to chest
• Gemzar (w/prior XRT)
• Vinelrelbine
• MTX
• Mitomycin C interstitial pneumonitis

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Renal and Bladder Toxicity

• CDDP dose limiting
• Methotrexate acute tubular necrosis
• Mitomycin hemolytic uremic syndrome
• Ifosfamide renal and bladder
• Cytoxan bladder

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Liver Toxicity

• 5FU cholestatic jaundice with intra-arterial
  infusion
• MTX hepatititis / cirrhosis
• Mitomycin C vasoocclusive crisis
• Hydroyurea

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Neurologic Toxicity

• CDDP dose limiting
• Vincristine Vinblastine
• Ifosfamide central CNS depression
• 5FU cerebellar ataxia
• hexamehtylmelamine central and /or peripheral
• MTX central with intrathecal regimens
  encephalopaty (IV route)
• Taxol peripheral neuropathy

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Dermatologic

• 5FU hand/foot ( Palmar Plantar Erythrodesia )
  PPE
• Bleomycin desquamation
• Adriamycin - extravasation
• Actinomycin-D- extravasation
• Vincristine- extravasation
• Mitomycin-C- extravasation
• Vinblastine- extravasation
• VP-16 chemical phlebitis with rapid infusion
• Hydroxyurea
• Taxotere
• Gemzar
• Melphalan skin rash
• MTX

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Occular

• CDDP- retinal dysfunction, cortical blindness
• 5FU - blepharitis, conjuntivitis, optic neuropathy

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Constipation

• Vincristine
• Ifosfamide

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Leukemia

• Platinum agents
• Mustard agents (10 incidence if given for over 1
  year)
• Etoposide (1 incidence)

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Dose Reduction Necessary

• Renal Failure
• Bleomycin
• Cyclophosphamide reduce 50 if renal failure
• Etoposide
• Topotecan
• Methotrexate
• Cisplatin (if CrCl
• Carbo (dose based on creatinine clearance using
  AUC)
• Mitomycin C
• Ifosfamide
• Cytoxan
• Hydroxyurea
• Melphalan 15 renal
• VP-16 (45)

• Liver Failure
• Vincristine
• Vinblastine
• Doxorubicin
• Taxotere

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Unique Side Effects
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Palmar Plantar Erythrodeisia
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Fertility and Chemotherapy

• Freezing eggs
• Creation of embryos that can be frozen
• Storage of ovarian tissue
• Transplantation of ovaries

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Chemotherapy and Fertility

• Chemotherapeutic agents have been implicated in
  ovarian failure. These include alkylating agents,
  antimitotic antibiotics, and vinca alkaloids that
  directly affect mitosis as well as
  antimetabolites that affect DNA synthesis.
• Cyclophosphamide Gonadotoxic doses for
  prepubertal females occur at a cumulative dose of
  400 mg/kg, slightly higher than for postpubertal
  women, who are susceptible at doses of 200 to 300
  mg/kg.
• Doxorubicin seems to decrease fertility
• Vinca alkaloids (vincristine and vinblastine) and
  antimetabolites (fluorouracil, cytarabine, and
  methotrexate), both of which affect cell
  division, have not been associated with ovarian
  failure.
• Regardless of the chemotherapeutic agent used,
  patient age is the single most important
  determining factor for gonadal toxicity after
  exposure to chemotherapy.
• The older the patient at the time of
  administration of systemic chemotherapy, the
  greater the probability of permanent gonadal
  failure
• Multiple ethical issues are involved.

Alexander, Carolyn J. M.D. Tanner, Edward J.
M.D. Kolp, Lisa A. M.D. Fertility After Cancer
Therapy. Postgraduate Obstetrics Gynecology.
25(5)1-7, March 15, 2005.
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Dont get any bright ideas, we are done
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Treatment of Endometrial Cancer Stage 3 and 4
after Staging followed by the below regimens