High-dose cisplatin and vinblastine infusion with or without radiation therapy in patients with advanced non-small-cell lung cancer.

Abstract

Non-small-cell lung cancer (NSCLC) patients with locally advanced or metastatic measurable disease were given a combination of cisplatin, 200 mg/m2 divided in five daily doses, and simultaneously, vinblastine, 7.5 mg/m2 as a continuous intravenous (IV) infusion over five days. Five courses of chemotherapy were planned. Afterwards or on progression, patients were randomized to receive maximally tolerated radiation to all sites of disease v observation only. Forty males and seven females were entered. Median age was 60 years (range, 37 to 74), median Karnofsky performance status was 70 (range, 30 to 90). Five patients had previous brain radiation therapy for metastatic disease, all others were previously untreated. Side effects in the 87 courses of chemotherapy administered included leukopenia (WBC less than 1,000/microL following nine courses) and thrombocytopenia (platelets less than 20,000/microL following four courses). Ten patients became septic, nine of them while leukopenic. Elevations of serum creatinine followed eight courses; in all cases the level was less than 3.0 mg/dL. Nausea and vomiting were mild to moderate. Five patients experienced mild hypoacusis and six had sensory polyneuropathy. The deaths of three patients were considered drug-related. The response rate was 28%. The median survival for the group was 22 weeks, 63.2 weeks for responders and 17.9 weeks for nonresponders. Twenty-six patients received radiation therapy, 16 randomized to this arm as planned, ten to palliate symptoms. Median survival of all irradiated patients was 24.8 weeks. Seven responders to chemotherapy were randomized to receive radiotherapy; their median survival was 25 weeks. In six responders randomized not to receive radiation, the median survival was 77.8 weeks (P greater than .3). Among nonresponding patients, the median survival of those radiated was 22.2 weeks, while that of nonradiated patients was 11 weeks. This regimen is cumbersome and toxic. It has offered no major survival benefits, or improvement in response rates, therefore, we do not recommend it for the standard treatment of NSCLC.

Schedule-Dependent Interaction between Vinblastine and Cisplatin in Ehrlich Ascites Tumors in Mice

“…push, and the day of administration. Most of these clinical trials showed that the combination of Vinca alkaloids and CDDP did not produce a significant response rate or prolonged survival, and in many cases, increased toxicity was observed (Mulder et al, 1982;Fuks et al, 1983;Newman et al, 1983;Blumenreich et al, 1987;Fraschini et al, 1988). Two recent reports on salivary gland malignancies (Airoldi et al, 2001) and non-small-cell lung cancer (DePas et al, 2001) showed positive results of this schedule.…”

“…CDDP combined with several tubulin-binding agents is used in chemotherapeutic schedules for treatment of many different types of cancer, such as non-small-cell-lung cancer (Fuks et al, 1983;Blumenreich et al, 1987;DePas et al, 2001), urothelial cancer (Dodd et al, 1999), melanoma (Mulder et al, 1982), breast carcinoma (Fraschini et al, 1988), and small cell carcinoma of the lung (Newman et al, 1983). In most of the clinical reports on combined chemotherapeutic schedules in solid tumors, the exact data on sequence of particular drugs are not given.…”

“…Combined chemotherapy schedules including cisplatin [cisdiamminedichloroplatinum(II); CDDP] and various tubulinbinding agents are well established and are used for treatment of various malignancies, such as testicular cancer, lung cancer, and salivary gland, melanoma, and breast carcinomas (Auersperg et al, 1977;Mulder et al, 1982;Fuks et al, 1983;Newman et al, 1983;Huberman et al, 1986;Blumenreich et al, 1987;Creagan et al, 1987;Fraschini et al, 1988;Stefenelli et al, 1988;Haskell, 1990;Kosmidis et al, 1994;Eton et al, 1999;Airoldi et al, 2001;De Pas et al, 2001). Design of currently used combined chemotherapeutic schedules is based on data derived from preclinical studies, and Phase I and II clinical studies.…”

Comprehensive analysis of the putative competing endogenous RNA network in human lung adenocarcinoma

“…However, none of these drugs have been reported to be related to the treatment of lung cancer through interactions with TBXA2R. Nevertheless, there is much evidence indicating that iloprost [40], acetaminophen [41], morphine [42], furosemide [43], and vinblastine [44] are broadly applied in chemotherapy for lung cancer patients. Nevertheless, this study still provides novel insights into LUAD pathogenesis and treatment.…”