Cisplatin in lung cancer

Dimeric complexes like [Cl(NH3)Pt H2N(CH2)4NH2 Pt(NH3)Cl]Cl2 are also being investigated as they bind to DNA in a different way to that involved in cisplatin binding and are active in cisplatin-resistant human tumour cells. They are more potent than cisplatin in lung cancer models in vivo and are likely to go on clinical trials in the near future [204],... 

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... 

Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. New Engl J Med 2004 350(4) 351—360. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

Giaccone, G. et al., Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer a phase 111 trial-lNTACT, /. Clin. Oncol., 22, 777-784, 2004. 

Isla, D., Sarries, C., Rosell, R., et al. (2004) Single nncleofide polymorphisms and outcome in docetaxel-cisplatin-treated advanced non-smaU-ceU lung cancer. Ann. Oncol. 15,1194-1203. 

Han, J. Y., Lim, H. S., Shin, E. S., et al. (2006) Comprehensive analysis of UGTIA polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-ceU lung cancer treated with irinotecan and cisplatin. J. Clin. Oncol. 24, 2237-2244. 

Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999 340(4) 265-271. 

Early clinical studies clearly demonstrated that cisplatin could be administered safely and concurrently with radiation therapy (73-75). Early clinical trials that demonstrated the promise of the combination of cisplatin and radiation therapy included the treatment of brain tumors (76,77), head and neck tumors (78), malignant melanoma (79), and bladder cancer (80). Early clinical trial integrating carboplatin administration with radiation therapy was carried out in patients with locally advanced nonsmall cell lung cancer (NSCLC) (81). A hypothesis put forth by Coughlin and colleagues (81) was that the best clinical outcomes would be achieved with the combination of cisplatin and radiation therapy in tumors that were responsive to cisplatin. 

The earliest combination chemotherapy and radiation trials in nonsmall-cell lung cancer included cisplatin and 5-fluorouracil and concurrent radiation therapy and found survival results comparable to those for sequential chemotherapy and radiation or to daily cisplatin and radiation therapy without surgery (119,121). Phase II studies of stage Ilia and Illb nonsmall-cell lung cancer patients treated with the combination of cisplatin with etoposide and 5 -fluorouracil and either single daily radiation fractionation or twice daily radiation fractionation prior to surgery produced similar clinical results (119,121). Complete surgical resection was accomplished in 70% of the patients, the median survival was 22 mo and the 2-yr survival rate was 45%. 

Weiden PL, Piantodosi S. Preoperative chemotherapy cisplatin and fluorouracil and radiation therapy in stage III non-small cell lung cancer A phase II study of the Lung Cancer Study Group. JNatl Cancer Oust 1991 83 266-272. 

Trovo MG, Minotel E, Fravelun G, et al. Radiotherapy versus radiotherapy enhanced by cisplatin in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys 1992 24 11-16. 

Ansari R, Tokara R, Fisher W, et al. A phase III study of thoracic irradiation with and without concomitant cisplatin in locally advanced unresectable non-small cell lung cancer, a Hoosier Oncology Group study. Proc Amer Soc Clin Oncol 1991 10 242. 

Ravasl G, Bodini AV, Milani F, et al. Continuous infusion of cisplatin and concurrent radiotherapy in non-resectable stage III lung cancer. Lung Cancer 1991 7 164. 

Bremnes RM, Sundstrom S, Aasebo U, Vilsvik J. Paclitaxel in combination with cisplatin, etoposide and thoracic radiotherapy for limited stage small cell lung cancer (SCLC) a phase II study (abstract 1826). ProAmSoc Clin Oncol 1998 17 475a. 

Kobayashi K, Shinbara A, Kamimura M, et al. Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer. Cancer Chemother Pharmacol 1998 42(1 ) 53—58. 

Goss G, Lochrin C, Perry G, et al. A phase I study of gemcitabine and Cisplatin with concurrent curative irradiation in Stage III Non-small cell lung cancer (NSCLC). Pro Am Soc Clin Oncol 1999 18 abstract 1986. 

Eagan RT, Ruud C, Lee RE, et al. Pilot study of induction therapy with cyclophosphamide, doxirubicin, and cisplatin (CAP) and chest irradiation prior to thoracotomy in initially inoperable stage III non-small lung cancer. Cancer Treat Rep 1987 71 895-900. 

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