Cisplatin In Squamous Cell Carcinoma Research Articles

A narrative review of genetic biomarkers in non-small cell lung cancer: an update and future perspectives.

Lung cancer has long been the leading cause of cancer deaths in the United States. Lung cancer has a poor prognosis, and our understanding of who will maximally benefit from different therapies is incomplete. This article discusses genetic biomarkers that may help in this regard. From origin until February 25, 2022, PubMed database was searched for terms "non-small cell lung cancer", "genomics" and "biomarker", with special attention paid to literature published within the past 10 years. Search was language restricted to English. Additional literature was identified through hand searches of the references of retrieved literature. The most robustly described biomarkers for non-small cell lung cancer (NSCLC) are assessment of specific gene mutations. These are currently used in clinical practice for both prediction and prognostication. Abnormal mutation status of STK11/LKB1 and KEAP1-NFE2L2 are associated with poor response to radiotherapy (RT), and STK11/LKB1 is further associated with resistance to PD-L1 immunotherapy. Abnormal TP53 is associated with decreased benefit from cisplatin in squamous cell carcinoma (SCC). In terms of prognostication, RB1 mutations are associated with decreased overall survival (OS) in NSCLC and KEAP1-NFE2L2 mutations are associated with increased local recurrence (LR).Additional work has focused on gene expression levels, as well as analysis of genetic factors and signaling molecules affecting the tumor microenvironment (TME). High levels of Rad51c and NFE2L2 are associated with resistance to chemotherapy, and high Rad51c levels are further associated with resistance to RT. High nuclear expression of β-catenin has additionally been associated with poor RT response. Further, there is increasing evidence that some long non-coding RNAs (lncRNAs) may play a crucial role in regulation of tumor radiosensitivity. Much of this work has had promising early results but will require further validation before routine clinical use. Finally, there is evidence that quantification of some signaling molecules and microRNAs (miRNAs) may have clinical utility in predicting adverse outcomes in RT. An improved understanding of tumor genetics in NSCLC has led to the development of targeted therapies and improved prognostication. As more work is done in this field, more and more genetic biomarkers will become candidates for clinical use. Much work will be required to validate these findings in the clinical setting.

Evaluation of safety of chemoradiotherapy with high-dose cisplatin for squamous cell carcinoma of the head and neck

Evaluation of safety of chemoradiotherapy with high-dose cisplatin for squamous cell carcinoma of the head and neck

Intra-arterial chemoradiation therapy with weekly low-dose cisplatin for squamous cell carcinoma of the maxillary sinus

A new intra-arterial chemoradiation regimen that involves infusing low-dose cisplatin in combination with definitive irradiation was used in 36 patients diagnosed with squamous cell carcinoma of the maxillary sinus. The safety and therapeutic efficacy of this regimen were reviewed retrospectively. An intra-arterial catheter was inserted in a retrograde manner into the target artery via the superficial temporal artery or occipital artery. Intra-arterial infusion was performed using cisplatin at a dose of 20–50mg/m2 per week for 6–8 weeks. At the same time, sodium thiosulphate was infused as a neutralizing agent. Irradiation was performed at 60Gy in 30 fractions. All 36 patients completed treatment. Grade 3 adverse events occurred in only seven patients (19.4%) and no grade 4 events were noted. As a primary therapy, the complete response rate was 83.3%, the partial response rate was 16.7%, and the overall response rate was 100%. The 2-year local control rate was 63.0%, and the 2-year overall survival rate was 75.5%. The 2-year preservation rate of the hard palate was 97.1%, that of the eyeball was 97.2%, and that of visual function was 94.4%. This treatment regimen can contribute to improving the quality of life of patients without reducing the curability of the therapy.

Indirect comparison of the efficacy of cetuximab and cisplatin in squamous cell carcinoma of the head and neck

Background:Cetuximab (Erbitux*Erbitux is a registered trade name of Bristol–Myers Squibb, Princeton, NJ, USA.) is the only new medical therapy for locally and regionally advanced SCCHN to be licensed in industrialized countries in the past 15 years and presents an alternative to cisplatin which is the current therapeutic standard. In the absence of a published head-to-head trial, we estimated the relative benefit of cetuximab and cisplatin using an indirect comparison methodology.Methods:We performed a systematic review of the Medline and Embase databases between 1998 and 2008 to find published trials of cisplatin plus radiotherapy vs. radiotherapy alone and synthesized the information with meta-analysis. Those results were combined with trial-based results of cetuximab plus radiotherapy vs. radiotherapy alone. Inclusion criteria stipulated that cisplatin be administered concurrently with radiation, the radiation protocol be comparable to the registration trial for cisplatin (once-daily, twice-daily, or concomitant boost) and cisplatin dosing be comparable to that in common use (i.e. day 1, 22 and 43 of treatment). Endpoints were locoregional control and overall survival. Two reviewers examined 269 abstracts which yielded four trials meeting the inclusion criteria.Results:There was little evidence of superiority of either platinum-based radiotherapy or cetuximab-based radiotherapy. All estimated hazard ratios were near 1.0 (equivalence), all confidence intervals spanned the null value (1.0), and no consistent pattern was observed regarding the direction of the effect. The results remained robust in sensitivity analysis.Conclusion:This is the first quantitative analysis allowing formal comparison between cetuximab and radiotherapy versus cisplatin and radiotherapy. Based on state-of-the-art methodology for indirect comparisons, it was not possible to identify either treatment regimen as superior in prolonging either locoregional control or overall survival. Until the publication of more studies, and particularly a head-to-head comparison, the two treatments may be considered equally efficacious when given alongside radiotherapy. The choice of treatment may focus on the toxicity profile of the medications.

Survivin shRNA Induces Caspase-3-Dependent Apoptosis and Enhances Cisplatin Sensitivity in Squamous Cell Carcinoma of the Tongue

Survivin is a member of the inhibitor of apoptosis protein (IAP) family; it is overexpressed in most cancer tissues and induces resistance to chemotherapy. In this study, we investigated whether a short hairpin RNA (shRNA) targeting survivin can induce apoptosis and enhance chemosensitivity to cisplatin in squamous cell carcinoma of the tongue. Results showed that chemosensitivity to cisplatin was surviving dependent in three cell lines (Tca8113, Bca885, and MCF7); higher survivin mRNA expression levels were associated with lower sensitivity to cisplatin. A plasmid-containing survivin shRNA was constructed and transfected into cell line Tca8113. Survivin shRNA inhibited expression of survivin mRNA and protein (63% and 65% inhibition, respectively), significantly inhibited cell proliferation, and enhanced chemosensitivity to cisplatin (p < 0.05). Apoptosis and caspase-3 activity were induced when cells were treated with survivin shRNA and/or cisplatin. Survivin shRNA induced caspase-3-dependent apoptosis and enhanced chemosensitivity to cisplatin in these tongue squamous cell carcinoma cell lines.

Randomized Phase II Trial of Concomitant Chemoradiotherapy Using Weekly Carboplatin or Daily Low-Dose Cisplatin for Squamous Cell Carcinoma of the Head and Neck

This randomized, phase II study aimed to compare concomitant chemoradiotherapy using weekly carboplatin or daily low-dose cisplatin as a treatment for squamous cell carcinoma of the head and neck. One hundred nineteen patients with moderate- to advanced-stage disease were eligible for the study. Fifty-three patients had stage II disease, 28 had stage III, and the remaining 38 had stage IV disease. Primary tumor sites included the larynx (N = 63), oropharynx (N = 30), hypopharynx (N = 23), and oral cavity (N = 3). Each patient received either a weekly carboplatin dose (100 mg/m(2)) in one arm or daily cisplatin (4 mg/m(2)) in the other arm for the initial 4 weeks of radiotherapy. The radiotherapy dose of 65 Gy was given in 26 fractions over 45 days, dependent on a good tumor response at 40 Gy. For ty-nine (81.7%) of 60 patients treated with carboplatin and 41 (69.5%) of 59 patients treated with cisplatin received the full dose of radiotherapy. Surgical-resection was optionally used for the remaining patients. The median follow-up time was 63 months. The local control rate at 5 years was 56.2% for the carboplatin-treated arm and 35.5% for the cisplatin-treated arm, respectively. The 5-year overall survival rate did not significantly differ between treatments: 71.4% for carboplatin and 66.0% for cisplatin. Hematologic toxicity was more frequent in the carboplatin-treated arm. No difference was observed in surgical complications or in radiation-related adverse effects. These findings suggest that weekly carboplatin treatment is preferable to daily low-dose cisplatin. This could be because the total dose of cisplatin was too low to be effective.

Measurement of platinum in saliva of patients treated with cisplatin.

A procedure for the measurement of platinum (Pt) in the saliva of patients treated with cisplatin has been developed. The saliva is collected and solubilized in hyamine hydroxide before analysis by graphite furnace atomic absorption spectrometry using assay by standard additions. The method has an analytical detection limit of 0.025 microgram/mL and is precise, with coefficients of variation of 3-10.0% over a range of 0.05-2.0 micrograms/mL. Platinum was measured in saliva collected during an 8-h infusion of cisplatin from five patients, at the end of a 30-min infusion in nine, and 24 and 48 h later from a further 15 patients, all of whom were treated with cisplatin for squamous cell carcinoma of the neck. The platinum concentration in saliva taken at the end of a 30-min infusion was 0.27 +/- 0.23 microgram/mL (mean +/- 1 SD) but was below the detection limit of 0.025 microgram/mL at 24 and 48 h. After an 8-h infusion the salivary Pt was significantly less (0.12 +/- 0.04 microgram/mL; P < 0.05). The plasma Pt concentrations after 30-min and 8-h infusions were 2.98 +/- 1.03 and 2.54 +/- 0.59 micrograms/mL, respectively, and were not significantly different. The results indicate higher concentrations of free platinum in plasma after 30 min compared with an 8-h infusion. The monitoring of salivary concentrations of platinum may therefore provide a non-invasive way to study the unbound fraction of cisplatin in blood and facilitate optimization of cisplatin treatment.

Successful treatment of cisplatin-induced hemolytic uremic syndrome with therapeutic plasma exchange

Cisplatin is a known cause of hemolytic uremic syndrome (HUS). The acute, fulminant form of cisplatin-induced HUS is almost always fatal. We present a 67-year-old Hispanic woman who was treated with cisplatin for squamous cell carcinoma of the tongue. Three days after receiving the treatment, she presented with increasing fatigue, decreased urine output, and confusion. Physical examination was remarkable for tachycardia of 130 beats/min, peripheral edema, and mental obtundation. Laboratory investigations showed a white cell count of 5,500/microL, hemoglobin level of 9.6 g/dL, hematocrit of 29.6%, and platelet count of 13,000/microL. Schistocytes were present on peripheral smear. Screening for disseminated intravascular coagulation was negative. Serum chemistry values included blood urea nitrogen 111 mg/dL, creatinine 3.8 mg/dL, and lactate dehydrogenase (LDH) 927 IU. The patient underwent hemodialysis and therapeutic plasma exchange (TPE), using fresh frozen plasma (FFP). Dialysis was no longer required after the fifth day. TPE was performed daily until the platelet count normalized on the 13th day, after which intertreatment intervals were extended until normalization of LDH levels on the 50th day. We conclude that the normally fatal, fulminant form of cisplatin-induced HUS can be successfully treated with standard TPE, using FFP replacement. (Am J Kidney Dis 1998 Aug;32(2):314-7)

Superselective intraarterial infusion of cisplatin for squamous cell carcinoma of the mouth: preliminary clinical experience.

The purpose of this study was to assess the initial clinical response to superselective intraarterial infusion of cisplatin for treating stage III and stage IV squamous cell carcinoma of the mouth. Thirteen patients received intraarterial cisplatin therapy. The tumors were located in the tongue (n = 7), gingiva (n = 3), buccal mucosa (n = 1), hard palate (n = 1), and floor of the mouth (n = 1). A coaxial technique was used to place microcatheters in the lingual, facial, inferior alveolar, buccinator, and distal internal maxillary arteries, depending on tumor location. The feeding vessels were identified by staining the tumor with infusion of indigocarmine dye in the selected vessel. Relatively low-dose cisplatin (30-40 mg/m2) was injected at the rate of 50 mg/hr. Two or three injections were performed, with a 1-week interval between injections. After chemotherapy, eight patients underwent surgery, four had radiation therapy, and one had both. Thirty-four intraarterial infusions were done successfully without any complications. Arterial infusion of indigocarmine dye was useful for exact identification of feeding vessels, especially when the tumor was extensive, at the margin of the arterial supply, or near the midline. The overall response rate was 92% (complete response [tumor completely resolved], 38%; partial response [tumor reduction > or = 50%], 54%). Ten of 13 patients had no recurrence from 4 to 19 months (mean, 10 months) after treatment. Two patients died of metastatic diseases 6 months after surgery or radiation therapy. One patient had local recurrence 8 months after surgery and postoperative irradiation. No systemic toxicity such as renal failure, liver dysfunction, or bone marrow suppression was observed. Mild and transient local toxicity such as edema or mucositis of the infused area was relatively common. Trigeminal neuralgialike symptoms and reduced mouth opening occurred in two cases and one case, respectively, probably due to direct toxicity to the peripheral trigeminal nerve and masticatory muscles, respectively. Superselective intraarterial infusion of low-dose cisplatin is feasible and safe and may have important applications in treating advanced carcinoma of the mouth.

Treatment of head and neck cancer with combination chemotherapy of CDDP and radiotherapy

There have been many reports on the usefuless of chemotherapy involving cisplatin for squamous cell carcinoma of the head neck. Single radiotherapy has also achieved excellent therapeutic results. In the present study, combined treatment involving multiple drug therapy (including cisplatin) and radiotherapy was carried out in 102 previously untreated patients with squamous cell carcinoma of the head and neck. The total efficiency rate of treatment involving cisplatin at a dose of 100mg or more per body weight and an X-ray dose of 40Gy or more was determined, along with assessment of differences among the total efficiency rate during the period of chemotherapy, the efficiency rate in Stages III and IV and the rate of complete regression (CR) for these stages. The patients who underwent the simultaneous, combined treatment showed a better efficiency rate and CR rate than the patients who underwent the single treatment. These results indicate that the simultaneous, combined treatment was more effective than the single treatment from the viewpoint of the main purpose of combined treatment involving chemotherapy and radiotherapy, i.e., treatment of Stage III and IV carcinoma or radical cure.