Platinum-Sensitive Regimen: Intraperitoneal Cisplatin and Paclitaxel
Armstrong DK et al. N Engl J Med 2006;354:34–43
Walker JL et al. Gynecol Oncol 2006;100:27–32
GOG Protocol #0172
Note: Regimen for Stage III epithelial ovarian or peritoneal carcinoma optimally debulked with no residual mass greater than 1 cm in diameter after surgery. Suboptimally debulked disease should not be treated with this regimen
Premedication for paclitaxel:
Dexamethasone 10 mg/dose; administer orally for 2 doses 12 hours and 6 hours before paclitaxel, or
Dexamethasone 20 mg/dose; administer intravenously over 10–15 minutes, 30–60 minutes before paclitaxel (total dose/cycle = 20 mg)
Diphenhydramine 50 mg; administer by intravenous injection 30 minutes before paclitaxel
Cimetidine 300 mg (or ranitidine 50 mg, famotidine 20 mg, or an equivalent histamine receptor [H2]-subtype antagonist); administer intravenously over 15–30 minutes, 30–60 minutes before paclitaxel
Paclitaxel 135 mg/m2; administer intravenously in a volume of 0.9% sodium chloride injection (0.9% NS) or 5% dextrose injection (D5W) sufficient to produce a concentration within the range 0.3–1.2 mg/mL, over 24 hours on day 1, every 21 days, for 6 cycles (total dosage of paclitaxel intravenously/cycle = 135 mg/m2)
Intraperitoneal cisplatin
Hydration before cisplatin: ≥1000 mL 0.9% NS; administer by intravenous infusion over a minimum of 2–4 hours
Note: If a large amount of ascites is present, it should be drained prior to the instillation of cisplatin
Cisplatin 100 mg/m2; administer intraperitoneally as rapidly as possible in warmed (37°C [98.6°F]) 0.9% NS 2000 mL through an implanted peritoneal catheter on day 2, every 21 days, for 6 cycles (total dosage/21-day cycle = 100 mg/m2). Following the infusion, patients alternate position from prone, supine, and left and right lateral decubitus every 15 minutes over 2 hours to maximize drug distribution throughout the peritoneal cavity
Note: Do not attempt to retrieve the infusate
Hydration after cisplatin: ≥1000 mL 0.9% NS; administer by intravenous infusion over a minimum of 3–4 hours. Also encourage high oral fluid intake. Goal is to achieve a urine output of ≥100 mL/hour
Intraperitoneal paclitaxel
Note: If a large amount of ascites is present, it should be drained prior to the instillation of paclitaxel
Paclitaxel 60 mg/m2; administer intraperitoneally as rapidly as possible in warmed (37°C [98.6°F]) 0.9% NS or D5W 1000 mL through an implanted peritoneal catheter, followed by an additional 1000 mL of 0.9% NS or D5W on day 8, every 21 days, for 6 cycles (total dosage of paclitaxel administered intraperitoneally/21-day cycle = 60 mg/m2)
Note: Do not attempt to retrieve the infusate
Systemic cisplatin
If intraperitoneal therapy is discontinued, substitute:
Cisplatin 75 mg/m2; administer intravenously in 250 mL 0.9% NS over 30–60 minutes on day 2, every 21 days, for 3 cycles (total dosage/cycle = 75 mg/m2)
Supportive Care
Antiemetic prophylaxis
Emetogenic potential on days 1 and 8 is LOW
Emetogenic potential on day 2 is HIGH. Potential for delayed symptoms
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis is NOT indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Arthralgia and myalgia G ≦2 associated with chemotherapy
Dexamethasone 4–8 mg/dose orally twice daily for 6 doses after chemotherapy
Patient Population Studied
A study of 205 women with Stage III epithelial ovarian or peritoneal carcinoma optimally debulked with no residual mass greater than 1 cm in diameter after surgery. All patients had a Gynecologic Oncology Group (GOG) performance status of 0–2
Notes
Among all randomized phase III trials conducted by the GOG among patients with advanced ovarian cancer, this therapy yielded the longest median survival (65.6 months)
Only 42% of patients received all 6 cycles of intraperitoneal therapy
The primary reason for discontinuation of intraperitoneal therapy was catheter-related complications
Among 205 patients randomly allocated to the intraperitoneal arm, 58% (119) did not complete all 6 cycles of intraperitoneal therapy. Of these 119 patients, 34% (40/119 = 34%) discontinued intraperitoneal therapy primarily as a result of catheter complications, whereas 29% (34/119 = 29%) discontinued for unrelated reasons. Additionally, 37% (45/119 = 37%) discontinued for reasons that were possibly related to the intraperitoneal treatment (see table under toxicities)
Hysterectomy, appendectomy, small bowel resection, and ileocecal resection were not associated with failure to complete 6 cycles
There appears to be an association between rectosigmoid colon resection and the ability to initiate intraperitoneal therapy. Intraperitoneal therapy was not initiated 16% of patients who had a left colon or rectosigmoid colon resection versus 5% of those who did not have such a resection (p = 0.015)
Intraperitoneal therapy should begin as soon as possible after surgery. A delay of intraperitoneal therapy allows opportunity for adhesions to develop and may limit intraperitoneal distribution of the IP fluid
The 2 L of intraperitoneal fluid administered with the intraperitoneal therapy does not replace the need for intravascular hydration administration and adequate urine output. Administration of at least 1 L of 0.9% sodium chloride injection both prior to and after cisplatin is essential
Armstrong DK et al. N Engl J Med 2006;354:34–43
Walker JL et al. Gynecol Oncol 2006;100:27–32