Cisplatin cervical cancer

Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999 340(15) 1144—1153. 

ChenMD, Paley PJ, PotishRA, Twiggs LB. Phase I trial of taxol as a radiation sensitizer with cisplatin in advanced cervical cancer. Gynecol Oncol 1997 67(2) 131-136. 

Cisplatin was first used to treat advanced cervical cancer shortly after the drug was introduced into clinical practice in the early 1970s. Although cisplatin continues to be one of the most active agents against cervical cancer, response rates are less than 30% for patients with recurrent or metastatic disease, and complete responses are rare and usually of short duration (14). 

Results of Prospective Randomized Trials that Compared Neoadjuvant Cisplatin-Containing Chemotherapy Followed by Radiation Therapy with Radiation Therapy Alone in Patients with Locally Advanced Cervical Cancer (52)... 

North American prospective trials of radiation sensitizers for cervical cancer have focused on the use of cisplatin, fluorouracil, and hydroxyurea. However, a number of other drugs also hold promise as effective radiation sensitizers for cervical cancer, including mitomycin C, epirubicin, paclitaxel, and carboplatin. 

Other potential radiation sensitizers for cervical cancer are being explored in phase I and II trials. Paclitaxel has been combined with cisplatin in several small phase I studies. Pignata et al. (29) found that 50 mg/m2 per week of paclitaxel could be combined with weekly cisplatin (30 mg/m2) and radiation therapy with acceptable toxicity, although 10 of 18 patients in their study had grade 3-4 hematologic toxicity. Chen etal. (30) also were able to give weekly paclitaxel at a dose of 50 mg/m2 (in this case combined with 50 mg/m2 of cisplatin every three weeks) with tolerable toxicity and minimal delay in planned radiation therapy. In both studies, the dose-limiting side effect appeared to be diarrhea. It should be noted that the total dose of cisplatin delivered in these trials was lower than that used in the most successful prospective trials of cisplatin or cisplatin and fluorouracil (Table 3). 

Although a number of other agents are of interest as possible radiation sensitizers, most investigators find it difficult to justify testing them in potentially curable cervical cancer patients without including cisplatin because of the dramatic improvements documented when cisplatin was used in the prospective randomized trials described earlier in this chapter. 

Tattersall MHN, Larvidhaya V, Vootiprux V, et al. Randomized trial of epirubicin and cisplatin chemotherapy followed by pelvic radiation in locally advanced cervical cancer. Am J Clin Oncol 1995 13 444-451. 

A 35-year-old female is being treated for cervical cancer with cis-platin. Of the following, how is cisplatin classified ... 

The in vitro antitumor activity of curcumin in HPV-associated cells has been established [Roy et al., 2002]. Curcumin modulates the in vitro expression and function of Pgp in multidrug-resistant human KB-V1 cells [Anand et al., 2008 Chearwae et al., 2004] and sensitizes cisplatin-resistant SiHa cells to cisplatin-induced apoptosis [Venkatraman et al., 2005], indicating its ability to reverse MDR in cervical cancer cells. The effect of curcumin in HPV-associated cells was found to involve the down-regulation of viral oncogenes, NF-kB and AP-1 [Anand et al., 2008 Divya and Pillai, 2006],... 

Cervical and Endometrial Cancer. Cisplatin is one of the most active agents available for the treatment of squamous-cell cancers of the cervix. Single-agent trials have indicated response rates of up to 31% in patients with advanced disease, with nearly one-third being complete responses [186], The GOG reported the results of a large (394 patients) randomized trial in 1989 comparing carboplatin and iproplatin monotherapy and noted a 15% response rate with carboplatin, suggesting that its activity may not be comparable to cisplatin in cervical cancer [187]. 

Marked increments in response were observed with the incorporation of cisplatin into combination regimens response rates greater that 50% were reported in Phase-Ill studies of cisplatin/ifosfamide, cisplatin/ifosfamide/ bleomycin, and cisplatin/5-FU [188-190]. Randomized trials of these combinations administered prior to radiotherapy in locally advanced disease have not shown a survival advantage however, a recent GOG trial of concurrent cisplatin or cisplatin/5-FU/hydroxyurea and radiation was associated with significantly improved progression-free survival versus concurrent hydroxyurea and radiation in patients with Stage IIB-IVA cervical cancers [191]. Combined cisplatin and paclitaxel produced responses in 9 of 11 patients in a recent GOG study [192] and will be the focus of larger trials in the future. 

In a phase-II study, 14 patients with metastatic cervical cancer or recurrent disease not eligible for surgery or radiation received bryostatin 1 50-65 pg/m -I- cisplatin 50mg/m. The most common adverse effects were myalgia, anemia, and nausea or vomiting one patient had a hypersensitivity reaction and one developed grade 3 nephrotoxicity (9). 

There are many drugs in this group of anti-cancer drugs. Some other examples are busulphan (for leukaemia), carmustine (for brain mmours), treosulphan (for ovarian cancer) and cisplatin (for lung, testicular, bladder, ovarian and cervical cancers). 

Preliminary biological screening pointed out that the toxicity of these systems upon light irradiation is comparable to that of cisplatin towards cervical cancer cells (HeLa). ... 

Using a short-term ATP bioluminescence assay Boike et al. (1990) studied the ability of two me-thylxanthines (caffeine and pentoxifylline) and an inhibitor of ADP-ribosyltransferase (3-aminobenz-amide) to enhance cisplatin cytotoxicity in gynaecological cancer cell lines. Pentoxifylline enhanced cisplatin cytotoxicity in both the human cervical cancer cell line ME-180 and the human ovarian cancer cell line CAOV-3. Increasing concentrations of pentoxifylline, while relatively nontoxic to both cell lines, produced a concentration-dependent enhancement of cisplatin cytotoxicity. 

I.V. Chemotherapy Plus Radiation (Chemoradiation) In a multi-institutional study reported in 1999 by Morris et al. of MDACC, the effects of radiation therapy to the pelvic and paraaortic field were compared to that of pelvic irradiation and concurrent chemotherapy with 5FU and cisplatin in women with advanced cervical cancer. The estimated cumulative rates of survival at 5 years were 73% among patients treated with radiotherapy and chemotherapy and 58% among patients treated with radiotherapy alone. Because of the success of chemoradiation in the management... 

Sahin K, Tuzcu M, Basak N, Cagfayan B, Kilic U, Sabin F, Kucuk O (2012) Sensitization of cervical cancer cells to cisplatin by genistein The role of NFkappaB and Akt/mTOR signaling pathways. J Oncol 2012 461562... 

Candelaria M, Garcia-Arias A, Cetina L, Duefias-Gonzalez A. Radio sensitizers in cervical cancer cisplatin and beyond. Radiat Oncol 2006 1 15-32. 

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