Chemotherapy in epithelial ovarian cancer. Dr.Azarm.

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Transcript of Chemotherapy in epithelial ovarian cancer. Dr.Azarm.

Page 1: Chemotherapy in epithelial ovarian cancer. Dr.Azarm.
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‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍Chemotherapy‍‍‍‍in‍‍‍‍epithelial‍‍‍‍ovarian‍‍‍‍

cancer. Dr.Azarm

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Recommendation — platinum agents (especially carboplatin) plus paclitaxel, carboplatin plus paclitaxel is the standard of care for EOC The regimen I use is paclitaxel 175 mg/m2 over three hours plus carboplatin AUC 6 to 7.5 (starting with the higher dose), every three weeks for six

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Taxanes‍‍‍‍plus‍‍‍‍platinum‍‍‍‍agents:    The regimen of paclitaxel (135 mg/m2 over 24 hours) immediately followed by cisplatin (75 mg/m2) offers the best therapeutic ratio, and initial studies ameliorated concerns for overlapping neurotoxicity

Dr.Azarm

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Carboplatin‍‍‍‍plus‍‍‍‍docetaxel:

Docetaxel may represent a less toxic alternative to paclitaxel.

Dr.Azarm

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Recommendation : Based‍‍‍‍upon‍‍‍‍the‍‍‍‍favorable‍‍‍‍safety‍‍‍‍profile‍‍‍‍of‍‍‍‍platinum‍‍‍‍agents‍‍‍‍(especially‍‍‍‍carboplatin)‍‍‍‍plus‍‍‍‍paclitaxel.

The‍‍‍‍regimen‍‍‍‍doses‍‍‍‍are‍‍‍‍paclitaxel‍‍‍‍175‍‍‍‍mg/m2‍‍‍‍over‍‍‍‍three‍‍‍‍hours‍‍‍‍plus‍‍‍‍carboplatin‍‍‍‍AUC‍‍‍‍6‍‍‍‍to‍‍‍‍7.5‍‍‍‍(starting‍‍‍‍with‍‍‍‍the‍‍‍‍higher‍‍‍‍dose),‍‍‍‍every‍‍‍‍three‍‍‍‍weeks‍‍‍‍for‍‍‍‍six‍‍‍‍cycles.‍‍‍‍

For‍‍‍‍women‍‍‍‍with‍‍‍‍advanced‍‍‍‍disease‍‍‍‍(stage‍‍‍‍III‍‍‍‍and‍‍‍‍IV‍‍‍‍with‍‍‍‍either‍‍‍‍small‍‍‍‍volume‍‍‍‍of‍‍‍‍large‍‍‍‍volume‍‍‍‍disease),‍‍‍‍response‍‍‍‍rates‍‍‍‍approach‍‍‍‍90‍‍‍‍percent,‍‍‍‍with‍‍‍‍75‍‍‍‍percent‍‍‍‍achieving‍‍‍‍a‍‍‍‍clinical‍‍‍‍complete‍‍‍‍response.‍‍‍‍

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Maintenance‍‍‍‍therapy :

-Focused upon extending the duration of induction chemotherapy-Prolonged administration‍‍‍‍of‍‍‍‍single‍‍‍‍agents‍‍‍‍‍‍‍‍Chemotherapy -IP chemotherapy , -Hormonal agents , -Immunotherapy .

None of these strategies has been shown to improve outcomes

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Intraperitoneal‍‍‍‍chemotherapy‍‍‍‍:

‍‍‍‍IP‍‍‍‍therapy‍‍‍‍can‍‍‍‍permit‍‍‍‍a‍‍‍‍several-fold‍‍‍‍increase‍‍‍‍in‍‍‍‍drug‍‍‍‍concentration‍‍‍‍in‍‍‍‍the‍‍‍‍abdominal‍‍‍‍cavity‍‍‍‍compared‍‍‍‍to‍‍‍‍systemic‍‍‍‍administration‍‍‍‍.

IP‍‍‍‍cisplatin

IP‍‍‍‍paclitaxel

IP‍‍‍‍chemotherapy‍‍‍‍is‍‍‍‍benefit‍‍‍‍in‍‍‍‍a‍‍‍‍subset‍‍‍‍of‍‍‍‍women‍‍‍‍with‍‍‍‍optimally‍‍‍‍cytoreduced‍‍‍‍EOC‍‍‍‍(to‍‍‍‍<0.5‍‍‍‍cm),‍‍‍‍

IP‍‍‍‍chemotherapy‍‍‍‍should‍‍‍‍not‍‍‍‍be‍‍‍‍considered‍‍‍‍standard‍‍‍‍therapy,‍‍‍‍and‍‍‍‍used‍‍‍‍only‍‍‍‍in‍‍‍‍the‍‍‍‍context‍‍‍‍of‍‍‍‍a‍‍‍‍clinical‍‍‍‍trial.‍‍‍‍

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Stem‍‍‍‍cell-supported‍‍‍‍high‍‍‍‍dose‍‍‍‍chemotherapy

- Response rates are initially high, but short lived (usually six to nine months)

-There is no convincing evidence of a long-term survival benefit

-Women undergoing transplant with platinum-resistant bulky disease do particularly poorly

‍‍‍‍prognosis.

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NEOADJUVANT‍‍‍‍CHEMOTHERAPY‍‍‍‍VERSUS‍‍‍‍INITIAL‍‍‍‍SURGICAL‍‍‍‍DEBULKING:

Primary surgical cytoreduction followed by systemic chemotherapy is the preferred initial management for women with stage III or IV EOC.

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CONCLUSIONS‍‍‍‍AND‍‍‍‍RECOMMENDATIONS :

The combination of a platinum (usually carboplatin) and paclitaxel is standard therapy for the first-line treatment of women with EOC who require systemic chemotherapy. For women with advanced disease (stage III and IV with either small volume of large volume disease), response rates approach 90 percent, with 75 percent achieving a clinical complete response.

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Treatment‍‍‍‍of‍‍‍‍germ‍‍‍‍cell‍‍‍‍

tumors‍‍‍‍of‍‍‍‍the‍‍‍‍ovary

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All women with nondysgerminomatous germ cell malignancies, except those with unruptured stage IA disease, grade 1 immature teratomas should receive postoperative adjuvant chemotherapy.

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Patients with stage II or III disease)GST) who have a complete tumor resection and adjuvant chemotherapy will almost always remain free of recurrence .

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VAC (vincristine, actinomycin-D, and cyclophosphamide)

PVB(cisplatin, vinblastine, and bleomycin)

both had good activity against the various germ cell malignancies .

Choice‍‍‍‍of‍‍‍‍regimen‍‍‍‍‍‍‍‍in‍‍‍‍GST‍‍‍‍‍‍‍‍of‍‍‍‍‍‍‍‍Ovary‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍:

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Management‍‍‍‍of‍‍‍‍immature‍‍‍‍teratomas

Several reports support the successful management of these patients with surgery alone .

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MANAGEMENT‍‍‍‍OF‍‍‍‍ADVANCED‍‍‍‍DISEASE

Patients with incompletely resected metastatic ovarian GCTs should receive cisplatin-based combination chemotherapy.

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PEB‍‍‍‍cisplatin‍‍‍‍20‍‍‍‍mg/m2‍‍‍‍days‍‍‍‍one‍‍‍‍through‍‍‍‍‍‍‍‍5‍‍‍‍‍‍‍‍days‍‍‍‍,‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍

etoposide‍‍‍‍100‍‍‍‍mg/m2‍‍‍‍days‍‍‍‍one‍‍‍‍through‍‍‍‍five,‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍both‍‍‍‍every‍‍‍‍21‍‍‍‍days‍‍‍‍,‍‍‍‍

‍‍‍‍bleomycin‍‍‍‍30‍‍‍‍units‍‍‍‍weekly) for‍‍‍‍ three‍‍‍‍ to‍‍‍‍ four‍‍‍‍ courses‍‍‍‍ has‍‍‍‍ become‍‍‍‍ the‍‍‍‍ standard‍‍‍‍regimen for‍‍‍‍patients‍‍‍‍with‍‍‍‍advanced‍‍‍‍ovarian‍‍‍‍GCT,‍‍‍‍and‍‍‍‍long-term‍‍‍‍survival‍‍‍‍can‍‍‍‍be‍‍‍‍expected‍‍‍‍in‍‍‍‍60‍‍‍‍to‍‍‍‍80‍‍‍‍percent‍‍‍‍of‍‍‍‍cases‍‍‍‍.

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Etoposide (120 mg/m2 on days 1 through 3),‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍‍Carboplatin (600 mg/m2 on day 2), and Bleomycin (15 mg/m2 on day 3), with courses administered every 3 to 4 weeks until remission, and then two more courses. With a median follow-up of 53 months, the five-year survival and event-free survival rates were 91 and 88 percent,

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Cisplatin-based‍‍‍‍chemotherapy‍‍‍‍is‍‍‍‍highly‍‍‍‍effective‍‍‍‍for‍‍‍‍advanced‍‍‍‍(incompletely‍‍‍‍resected‍‍‍‍or‍‍‍‍recurrent)‍‍‍‍dysgerminoma‍‍‍‍

ysgerminoma:d

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LATE‍‍‍‍EFFECTS‍‍‍‍OF‍‍‍‍TREATMENT :

-renal and gonadal dysfunction, -neurotoxicity, -cardiovascular toxicity, and -secondary malignancies

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