A randomized comparative trial of carboplatin and iproplatin in advanced squamous carcinoma of the uterine cervix: a Gynecologic Oncology Group study.

Abstract

A total of 394 patients with advanced, measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were randomized to therapy with either carboplatin or iproplatin. There were 23 patients ineligible for the study and 10 patients who were not evaluable; the remaining 361 patients were evaluable for response and adverse effects. Randomization was well balanced for age, performance status, and prior therapy. Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin (340 mg/m2 if the patient underwent prior radiation) and 270 mg/m2 for iproplatin (230 mg/m2 if the patient underwent prior radiation). These doses are equivalent to cisplatin doses of 75 to 100 mg/m2. Hematologic toxicity was dose-limiting, among which thrombocytopenia was slightly more common than leukopenia. Gastrointestinal toxicity was also prominent with both agents; however, iproplatin was significantly more toxic than carboplatin (P less than .001). Renal, otic, and peripheral nervous system toxicities were absent or infrequent with both analogs. No electrolyte abnormalities were observed. The percentage of planned dosages that were actually administered was 100% of carboplatin doses and 85% of iproplatin doses (P less than .0001). The reduction in iproplatin dose was apparently due to gastrointestinal toxicity. Response rates were similar for both agents (15% for carboplatin, 11% for iproplatin) and appear to be inferior to those noted with the parent compound, cisplatin.

HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer

“…This is noteworthy because cell membrane transport proteins have been shown to be critical determinants of platinum drug sensitivity/resistance, possibly as a result of secreted factors from MSCs which can affect transport characteristics. Lending further credence to our data, in cervical cancer (a disease which is known to expresses high levels of HOTAIR [ 34 ]) carboplatin has been repeatedly reported to be a less effective platinum analog than cisplatin [ 35 – 37 ].…”

HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer

“…This is noteworthy because cell membrane transport proteins have been shown to be critical determinants of platinum drug sensitivity/resistance, possibly as a result of secreted factors from MSCs which can affect transport characteristics. Lending further credence to our data, in cervical cancer (a disease which is known to expresses high levels of HOTAIR [ 34 ]) carboplatin has been repeatedly reported to be a less effective platinum analog than cisplatin [ 35 – 37 ].…”

Phase I-II study of carboplatin vincristine methotrexate and bleomycin (COMB) in carcinoma of the cervix

“…Carboplatin and cisplatin appear to have equal antitumour activity as single agents against ovarian carcinoma (Wiltshaw, 1985;Canetta et al, 1985), but recent data suggest that carboplatin may be less effective than cisplatin against cervical carcinoma (McGuire et al, 1988;Bonomi et al, 1985). This probably explains the low response rate of COMB.…”

Radiation with cisplatin or carboplatin for locally advanced cervix cancer: The experience of a tertiary cancer centre

“…Carboplatin is often substituted for cisplatin and has been demonstrated to have equivalent efficacy in certain malignancies such as epithelial ovarian cancer. In women with metastatic cervical cancer, it is considered that cisplatin rather than carboplatin is more effective based on the GOG77 protocol that tested the efficacy of single agent platinum analogues (carboplatin and iproplatin) . While this study did not directly compare these platinum analogues with cisplatin, the observed response rates of 10–15% did not compare favourably with previous studies of cisplatin, which were associated with response rates of up to 38% in phase II studies .…”

HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer

“…This is noteworthy because cell membrane transport proteins have been shown to be critical determinants of platinum drug sensitivity/resistance, possibly as a result of secreted factors from MSCs which can affect transport characteristics. Lending further credence to our data, in cervical cancer (a disease which is known to expresses high levels of HOTAIR [ 34 ]) carboplatin has been repeatedly reported to be a less effective platinum analog than cisplatin [ 35 – 37 ].…”

Phase I-II study of carboplatin vincristine methotrexate and bleomycin (COMB) in carcinoma of the cervix

“…Carboplatin and cisplatin appear to have equal antitumour activity as single agents against ovarian carcinoma (Wiltshaw, 1985;Canetta et al, 1985), but recent data suggest that carboplatin may be less effective than cisplatin against cervical carcinoma (McGuire et al, 1988;Bonomi et al, 1985). This probably explains the low response rate of COMB.…”

Radiation with cisplatin or carboplatin for locally advanced cervix cancer: The experience of a tertiary cancer centre

“…Carboplatin is often substituted for cisplatin and has been demonstrated to have equivalent efficacy in certain malignancies such as epithelial ovarian cancer. In women with metastatic cervical cancer, it is considered that cisplatin rather than carboplatin is more effective based on the GOG77 protocol that tested the efficacy of single agent platinum analogues (carboplatin and iproplatin) . While this study did not directly compare these platinum analogues with cisplatin, the observed response rates of 10–15% did not compare favourably with previous studies of cisplatin, which were associated with response rates of up to 38% in phase II studies .…”

HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer

“…This is noteworthy because cell membrane transport proteins have been shown to be critical determinants of platinum drug sensitivity/resistance, possibly as a result of secreted factors from MSCs which can affect transport characteristics. Lending further credence to our data, in cervical cancer (a disease which is known to expresses high levels of HOTAIR [ 34 ]) carboplatin has been repeatedly reported to be a less effective platinum analog than cisplatin [ 35 – 37 ].…”

Phase I-II study of carboplatin vincristine methotrexate and bleomycin (COMB) in carcinoma of the cervix

“…Carboplatin and cisplatin appear to have equal antitumour activity as single agents against ovarian carcinoma (Wiltshaw, 1985;Canetta et al, 1985), but recent data suggest that carboplatin may be less effective than cisplatin against cervical carcinoma (McGuire et al, 1988;Bonomi et al, 1985). This probably explains the low response rate of COMB.…”

Radiation with cisplatin or carboplatin for locally advanced cervix cancer: The experience of a tertiary cancer centre

“…Carboplatin is often substituted for cisplatin and has been demonstrated to have equivalent efficacy in certain malignancies such as epithelial ovarian cancer. In women with metastatic cervical cancer, it is considered that cisplatin rather than carboplatin is more effective based on the GOG77 protocol that tested the efficacy of single agent platinum analogues (carboplatin and iproplatin) . While this study did not directly compare these platinum analogues with cisplatin, the observed response rates of 10–15% did not compare favourably with previous studies of cisplatin, which were associated with response rates of up to 38% in phase II studies .…”