Cisplatin neck cancers

The antitumor activity of titanocene dichloride 21 was first recognized in 1979 (150), and since then the activity of several other metallocenes (V, Nb, Mo, Fe, Ge, and Sn) has been reported (151). Most interest has centered on titanocene dichloride and on vanadocene dichloride 22, which are active against a diverse range of human carcinomas, including gastrointestinal and breast carcinomas, but not against head and neck cancers. There appears to be a lack of crossresistance between titanocene dichloride and cisplatin. 

Gonzalez-Larriba J, Garcia Carbonero I, Sastre Valera J, Perez Segura P, Diaz-Rubino E. Neoadjuvant therapy with cisplatin/fluorouracil vs cisplatin/UFT in locally advanced squamous cell head and neck cancer. Oncology (Huntingtj 1997 11(9 Suppl 10) 90-97. 

The initial combination modality clinical studies with cisplatin and fractionated radiation therapy was carried out in head and neck cancer with weekly cisplatin (120-160 mg/m2) and conventional single daily fraction radiation (95). In a follow-up intergroup study, patients were randomized to radiation therapy alone or to radiation therapy plus 20 mg/ m2/wk cisplatin (96). Both studies showed no major increase in normal tissue toxicity in the radiation field and showed an increase in response rate. There was no increase in complete response rate or in survival. Bachaud et al.(97) carried out a randomized study comparing radiation therapy alone with concurrent cisplatin (50 mg/m2) and radiation therapy in postoperative patients. This trial produced a significant reduction in local recurrence and improved disease-free survival with 59% of the patients receiving the full planned dose of cisplatin. 

Wheeler et al. (100,101) took another tack and treated patients with unresectable head and neck cancer with cisplatin (40 mg/m2) daily for 5 d per course for three cycles along... 

Marcial VA, Paj ak TF, Mohuiddin M, et al. ConComitant cisplatin chemotherapy and radiotherapy in advanced mucosal squamous cell carcinoma of the head and neck. Cancer 1990 66 1861-1868. 

Taylor SG, Murthy AK, Caldarelli DD, et al. Combined simultaneous cisplatin/5-FU infusion chemotherapy and split course radiation in head and neck cancer. J Clin Oncol 1989 7 846-856. 

Robbins KT, Kumar P, Regine WF, et al. Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer the Memphis experience. Int J Radiat Oncol Biol... 

In phase II studies with topotecan alone, there is cytotoxic activity in lung cancer with intermittent dose schedules (33), as well as in lung cancer patients with topoisomerase II refractory disease (34). In advanced head and neck cancer topotecan is well-tolerated and has single-agent activity similar to that of cisplatin, 5-fluorouracil, and methotrexate... 

A preliminary report on a randomized trial on 83 stage III or IV locally advanced squamous cell head and neck cancer (SCHNC) patients demonstrated improved 2-yr disease-free survival (65% vs 41%, p = 0.01) and increased rate of local control (85% vs 59%, p < 0.05) in the concomitant chemoradiation group (cisplatin 50 mg/m2 weekly) in comparison to radiation therapy alone (25). It should be noted that the DFS was improved overall in the concomitant arm despite 18% patients receiving only two-thirds of their scheduled dose of cisplatin as a result of nausea and vomiting. Mature results from this study have not been published to date. 

Adelstein DJ, Adams GL, Li Y. A phase III comparison of standard radiation therapy (RT) versus RT plus concurrent cisplatin (DDP) versus split-course RT plus concurrent DDP and 5-fluorouracil (5FU) in patients with unresectable squamous cell head and neck cancer (SCHNC), ProcAnnu Meet Am Soc Clin Oncol 2000 19 A 1624. 

Taylor SG, Murthy AK, Griem KL, et al. Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer 8-year analysis of results. HeadNeck 1997 19 684—691. 

Kish JA, Weaver A, Jacobs J, et al. Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck. Cancer 1984 53 1819-1824. 

Schrijvers D, Johnson J, Jiminez U, et al. Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group. J Clin Oncol 1998 16 1054-1059. 

Murphy B, Li Y, Celia D, et al. Phase III study comparing cisplatin (C) and 5-Fluorouracil (F) versus cisplatin and paclitaxel (T) in metastatic/recurrent head and neck cancer (MHNC). ProcAnnu Meet Am Soc Clin Oncol 2001 20 A894. 

Rishchin D, Peters L, Hicks R, et al. Phase I trial of concurrent tirapazamine, cisplatin, and radiotherapy in patients with advanced head and neck cancer. J Clin Oncol 2001 19 535-542. 

Khuri FR, Nemunaitis J, Ganly I, et al. A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 2000 6 879-885. 

Cisplatin Forms intrastrand and interstrand DNA cross-links binding to nuclear and cytoplasmic proteins Non-small cell and small cell lung cancer, breast cancer, bladder cancer, gastroesophageal cancer, head and neck cancer, ovarian cancer, germ cell cancer Nausea and vomiting Nephrotoxicity, peripheral sensory neuropathy, ototoxicity, nerve dysfunction... 

Os-platinum (cisplatin) binds to intracellular DNA, causing both interstrand and intrastrand cross-linking. It is a cell-cycle phase nonspecific agent. Os-platinum, which is ineffective orally, is used for testicular, bladder, and head and neck cancers. It precipitates nephrotoxicity, ototoxicity, and gastrointestinal injury. 

Cisplatin has major antitumor activity in a broad range of solid tumors, including non-small cell and small cell lung cancer, esophageal and gastric cancer, head and neck cancer, and genitourinary cancers, particularly testicular, ovarian, and bladder cancer. When used in combination regimens with vinblastine and bleomycin or etoposide and bleomycin, cisplatin-based therapy has led to the cure of nonseminomatous testicular cancer. 

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