Supra‐additive effect with concurrent paclitaxel and cisplatin in vulvar squamous cell carcinoma in vitro

Abstract

The effect of concurrent paclitaxel and cisplatin was tested in vitro in 5 vulvar squamous cell carcinoma (SCC) cell lines (UM-SCV-1A, -2, -4 and -7 and UT-SCV-3). Chemosensitivity was tested using the 96-well plate clonogenic assay. Paclitaxel concentrations used varied between 0.4 and 1.6 nM, and cisplatin concentrations varied between 0.1 and 0.9 g/ml. These drug concentrations are clinically achievable. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the 2 drugs with the survival fraction (SF) of paclitaxel alone. With all cell lines tested the growth-inhibitory effect of simultaneous paclitaxel and cisplatin was at least additive. The effect of the tested combination on the UM-SCV-1A and UT-SCV-3 cell lines was clearly supra-additive with all paclitaxel concentrations tested, and the UM-SCV-4 and UM-SCV-7 cell lines exhibited a supra-additive effect with increasing paclitaxel concentrations. The degree of supra-additivity was dose-dependent in the UM-SCV-7 cell line with increasing synergy at higher paclitaxel doses. In the current study the combination of paclitaxel and cisplatin had a clear additive or supra-additive cytotoxic effect on the vulvar SCC cell lines, and it has been successfully used in other gynecologic malignancies; therefore concurrent paclitaxel and cisplatin also deserves further testing in clinical settings in advanced-stage vulvar carcinoma, which has a poor prognosis.

Effect of Epidermal Growth Factor Receptor Inhibitor Alone and in Combination with Cisplatin on Growth of Vulvar Cancer Cells

“…To our knowledge, only a case report is available on the use of cisplatin as a single agent in vulvar carcinoma 30 . However, a number of in vitro studies have reported the effect of cisplatin on squamous cell carcinoma (SCC) including vulvar cancer 31–33 . Cisplatin primarily induces platination of DNA, leading to intrastrand and interstrand cross‐links 34 .…”

“…30 However, a number of in vitro studies have reported the effect of cisplatin on squamous cell carcinoma (SCC) including vulvar cancer. [31][32][33] Cisplatin primarily induces platination of DNA, leading to intrastrand and interstrand cross-links. 34 Recently, it has been shown that cisplatin exerts its anticancer effect by inducing apoptosis through the activation of JNK and p38 cascades.…”

Combination of paclitaxel and carboplatin as second‐line therapy for patients with metastatic melanoma

“…The PC combination for the treatment of MM patients has been investigated in two recently reported prospective trials (Table 3). 25, 26 The rationale for combining these agents has been: 1) platinum‐alkylating agents have been demonstrated to have a definite (though minor) degree of activity in melanoma16, 27–29; 2) taxanes were demonstrated in early clinical trials to have a minor activity in melanoma30–33; 3) in vitro and clinical data suggest synergy between these drugs when used in combination in a wide variety of tumors, including melanoma23, 24, 34–40; and 4) the toxicity profiles of these agents do not overlap. Early clinical trials testing the combination of paclitaxel with platinum agents in patients with a variety of diseases noted some responses among melanoma patients 23, 24, 27.…”

Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer

“…Raitanen et al [129] found that two of the three vulvar squamous carcinoma cell lines, having sublethal damage repair capacity, exhibited a trend toward loosing the repair capacity when exposed to TAX during the irradiation. In a further study, the combination of TAX and CDDP at concentrations that are clinically achievable (0.4-1.6 nM/ml and 0.1-0.9 g/ml, respectively) had a clear additive or synergistic cytotoxic effect on different vulvar squamous carcinoma cell lines [130]. Therefore, concurrent chemoradiation with TAX or TAX + CDDP deserves to be clinically assessed in patients with advanced vulvar cancer.…”