Modulation of platinum sensitivity and resistance by cyclosporin A in refractory ovarian and fallopian tube cancer patients: A phase II study

Setsuko K Chambers, Carol A. Davis, Peter E. Schwartz, Ernest I. Kohorn, Joseph T. Chambers

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Our objective was to assess the activity of cyclosporin A (CsA) used as a chemomodulator of carboplatin in refractory ovarian and fallopian tube cancer patients. Fifty-one patients (47 epithelial ovarian, 1 ovarian mixed mesodermal tumor, and 3 fallopian tube carcinomas) were enrolled in a prospective Phase II trial of CsA and carboplatin. CsA was infused as a loading dose of 10 mg/kg over 5 h, followed by carboplatin infused over 30 min at an AUC of 6 mg/ml x min, then a 24-h continuous infusion of 11.6 mg/kg CsA. The patients received this protocol as second- to sixth-line therapy and had received between 1 and 3 prior platinum-based regimens. Light patients received more than six cycles every 28 days, 34 patients received three to six cycles; and 9 patients received only one or two cycles. Thirty-eight patients were evaluable for objective response, and in an additional nine patients, CA-125 was the only marker of response. Four patients had no marker of disease. Of evaluable patients, 74% were platinum resistant. There were nine objective responses (one complete and eight partial responses) for an overall response rate in evaluable patients of 24%, with a median duration of response of 7 months (range, 3-38+ months). No responses were seen in patients who had received only one or two cycles of therapy. Among the strictly defined platinum-resistant patients, there was an overall 14% response rate, including one partial response seen after five prior regimens of chemotherapy including paclitaxel, and one ongoing complete response for 38+ months. Among the rest of the patients (those who were potentially platinum sensitive), there was an overall 50% response rate; four of five responses were seen in patients with a platinum-free interval of <24 months, with only one response seen in a patient with a platinum-free interval of > 24 months. Of evaluable patients, 34% had stable disease for a duration of 3-19 months. The most common grade 3 or 4 toxicity, thrombocytopenia, was seen in 22% of the patients. Hypertension, which responded to medications, was seen in 18% of the patients during the CsA infusion. We concluded that this CsA/carboplatin regimen is active in potentially platinum-sensitive patients and compares well with the expected response rate of 30% in patients with a platinum-free interval <24 months who are retreated with platinum. Moreover, this regimen had modest but real activity in platinum-resistant patients.

Original languageEnglish (US)
Pages (from-to)1693-1697
Number of pages5
JournalClinical Cancer Research
Volume2
Issue number10
StatePublished - Oct 1996
Externally publishedYes

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Fallopian Tube Neoplasms
Platinum
Cyclosporine
Carboplatin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Modulation of platinum sensitivity and resistance by cyclosporin A in refractory ovarian and fallopian tube cancer patients : A phase II study. / Chambers, Setsuko K; Davis, Carol A.; Schwartz, Peter E.; Kohorn, Ernest I.; Chambers, Joseph T.

In: Clinical Cancer Research, Vol. 2, No. 10, 10.1996, p. 1693-1697.

Research output: Contribution to journalArticle

Chambers, Setsuko K ; Davis, Carol A. ; Schwartz, Peter E. ; Kohorn, Ernest I. ; Chambers, Joseph T. / Modulation of platinum sensitivity and resistance by cyclosporin A in refractory ovarian and fallopian tube cancer patients : A phase II study. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 10. pp. 1693-1697.
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abstract = "Our objective was to assess the activity of cyclosporin A (CsA) used as a chemomodulator of carboplatin in refractory ovarian and fallopian tube cancer patients. Fifty-one patients (47 epithelial ovarian, 1 ovarian mixed mesodermal tumor, and 3 fallopian tube carcinomas) were enrolled in a prospective Phase II trial of CsA and carboplatin. CsA was infused as a loading dose of 10 mg/kg over 5 h, followed by carboplatin infused over 30 min at an AUC of 6 mg/ml x min, then a 24-h continuous infusion of 11.6 mg/kg CsA. The patients received this protocol as second- to sixth-line therapy and had received between 1 and 3 prior platinum-based regimens. Light patients received more than six cycles every 28 days, 34 patients received three to six cycles; and 9 patients received only one or two cycles. Thirty-eight patients were evaluable for objective response, and in an additional nine patients, CA-125 was the only marker of response. Four patients had no marker of disease. Of evaluable patients, 74{\%} were platinum resistant. There were nine objective responses (one complete and eight partial responses) for an overall response rate in evaluable patients of 24{\%}, with a median duration of response of 7 months (range, 3-38+ months). No responses were seen in patients who had received only one or two cycles of therapy. Among the strictly defined platinum-resistant patients, there was an overall 14{\%} response rate, including one partial response seen after five prior regimens of chemotherapy including paclitaxel, and one ongoing complete response for 38+ months. Among the rest of the patients (those who were potentially platinum sensitive), there was an overall 50{\%} response rate; four of five responses were seen in patients with a platinum-free interval of <24 months, with only one response seen in a patient with a platinum-free interval of > 24 months. Of evaluable patients, 34{\%} had stable disease for a duration of 3-19 months. The most common grade 3 or 4 toxicity, thrombocytopenia, was seen in 22{\%} of the patients. Hypertension, which responded to medications, was seen in 18{\%} of the patients during the CsA infusion. We concluded that this CsA/carboplatin regimen is active in potentially platinum-sensitive patients and compares well with the expected response rate of 30{\%} in patients with a platinum-free interval <24 months who are retreated with platinum. Moreover, this regimen had modest but real activity in platinum-resistant patients.",
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N2 - Our objective was to assess the activity of cyclosporin A (CsA) used as a chemomodulator of carboplatin in refractory ovarian and fallopian tube cancer patients. Fifty-one patients (47 epithelial ovarian, 1 ovarian mixed mesodermal tumor, and 3 fallopian tube carcinomas) were enrolled in a prospective Phase II trial of CsA and carboplatin. CsA was infused as a loading dose of 10 mg/kg over 5 h, followed by carboplatin infused over 30 min at an AUC of 6 mg/ml x min, then a 24-h continuous infusion of 11.6 mg/kg CsA. The patients received this protocol as second- to sixth-line therapy and had received between 1 and 3 prior platinum-based regimens. Light patients received more than six cycles every 28 days, 34 patients received three to six cycles; and 9 patients received only one or two cycles. Thirty-eight patients were evaluable for objective response, and in an additional nine patients, CA-125 was the only marker of response. Four patients had no marker of disease. Of evaluable patients, 74% were platinum resistant. There were nine objective responses (one complete and eight partial responses) for an overall response rate in evaluable patients of 24%, with a median duration of response of 7 months (range, 3-38+ months). No responses were seen in patients who had received only one or two cycles of therapy. Among the strictly defined platinum-resistant patients, there was an overall 14% response rate, including one partial response seen after five prior regimens of chemotherapy including paclitaxel, and one ongoing complete response for 38+ months. Among the rest of the patients (those who were potentially platinum sensitive), there was an overall 50% response rate; four of five responses were seen in patients with a platinum-free interval of <24 months, with only one response seen in a patient with a platinum-free interval of > 24 months. Of evaluable patients, 34% had stable disease for a duration of 3-19 months. The most common grade 3 or 4 toxicity, thrombocytopenia, was seen in 22% of the patients. Hypertension, which responded to medications, was seen in 18% of the patients during the CsA infusion. We concluded that this CsA/carboplatin regimen is active in potentially platinum-sensitive patients and compares well with the expected response rate of 30% in patients with a platinum-free interval <24 months who are retreated with platinum. Moreover, this regimen had modest but real activity in platinum-resistant patients.

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