Randomized trial of three combinations of cisplatin with vindesine and/or VP-16-213 in the treatment of advanced non-small-cell lung cancer.

Dhingra, Hari M.; Valdivieso, Manuel; Carr, David; Chiuten, Delia F.; Farha, Peter; Murphy, William K.; Spitzer, Gary; Umsawasdi, Theera

doi:10.1200/jco.1985.3.2.176

Cited by 73 publications

(15 citation statements)

References 11 publications

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“…Although radiotherapy is of palliative value, individual cytotoxic agents have only produced low objective response rates and those responses reported have been of short duration (Hoffman et al, 1983). During the past 20 years combination chemotherapy has been extensively tested in randomised multicentre and single institution studies though almost always without a no treatment control (Simes, 1985;Dhingra et al, 1985). In general, studies comparing different combinations have yielded relatively low response rates and very similar patterns of survival regardless of therapy.…”

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“…In general, studies comparing different combinations have yielded relatively low response rates and very similar patterns of survival regardless of therapy. During the past decade the introduction of more intensive chemotherapy, often based on cisplatin, has resulted in an apparent small improvement in survival and a modest increase in response to therapy, but at the expense of greater toxicity (Dhingra, 1985;Klastersky & Sculier, 1985). High dose cisplatin regimes were introduced following the randomised study in which Gralla et al (1981) demonstrated that a dose of 120 mg m-2 every 4 weeks was superior to a dose of 60 mg m-2 in the same schedule.…”

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A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer

Woods

Williams²,

Levi³

et al. 1990

Br J Cancer

150

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Summary The value of chemotherapy in advanced non-small cell lung cancer (NSCLC) remains contentious. Because of this two separate but very similar trials were set up in Australia and Southampton (UK). Two hundred and one patients with stage IIIb or IV NSCLC were randomly assigned to cisplatin 120 mg m 2 on days 1 and 29 and vindesine 3 mg m-2 weekly x 6 or to no chemotherapy. Both groups were eligible to receive radiotherapy or other palliative treatment as required. Of 188 evaluable patients, 97 received chemotherapy and 91 were in the control arm. Response was assessed between days 42 and 49. Responders continued chemotherapy at the same doses though cisplatin being given 6 weekly x 4 and the vindesine 2 weekly x 12. The overall response rate to chemotherapy was 28%; there were no significant differences according to major prognostic criteria. Although the overall survival of the chemotherapy group (median 27 weeks) was longer than that of the no chemotherapy group (median 17 weeks) this was not statistically significant (log rank P = 0.33). For patients without dissemination (IlIb), median survival was 45 weeks in the chemotherapy arm and 26 weeks in the non-chemotherapy (log rank P = 0.075). Toxicity was universal and frequently severe: of 17 patients discontinuing chemotherapy after one cycle, 13 did so because of unacceptable toxicity. This chemotherapy cannot be recommended as routine treatment. Further phase III studies of chemotherapy in advanced NSCLC should continue to use a no chemotherapy control and should also attempt to measure quality of life, an issue not addressed effectively in this or other recent trials.

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confidence: 99%

A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer

Woods

Williams²,

Levi³

et al. 1990

Br J Cancer

150

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“…44 Although CIS-based chemotherapy is considered a standard treatment for advanced NSCLC, CIS has been consistently associated with marked toxicity in several epidemiological studies. 45,46 In contrast, phenolic compounds present in the human diet have been used to doses of SQE (100 µg/mL) and CIS (0.3 µg/mL), individually and in combination. The second and the third passages in the absent of treatment were derived from treated primary spheres.…”

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confidence: 99%

Combination of Sasa quelpaertensis Nakai Leaf Extract and Cisplatin Suppresses the Cancer Stemness and Invasion of Human Lung Cancer Cells

Kim

et al. 2014

Integr Cancer Ther

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Lung cancer is the leading cause of cancer death worldwide, and most chemotherapeutic drugs have limited success in treating this disease. Furthermore, some drugs show undesirable side effects due to the enrichment of cancer stem cells (CSCs) that are present, leading to resistance to conventional chemotherapy and tumor relapse. CSCs possess self-renewal characteristics, aggressive tumor initiating activity, and ability to facilitate tumor metastasis. Therefore, development of nontoxic agents that can potentiate chemotherapy and eliminate CSCs would be highly desirable. In the present study, we investigated whether Sasa quelpaertensis leaf extracts (SQE) and cisplatin (CIS), individually or in combination, would exert anti-CSC and antimetastatic effect in H1299 and A549 human lung cancer cells. Following these treatments, cell growth, phosphorylation of phosphoinositide-3 kinase, and activation of the mammalian target of rapamycin were inhibited. Decreased serial sphere formation, clonogenicity, and expression of major stem cell markers, such as CD44 and SOX-2, in CD44 + cancer stem cells were also observed. In addition, inhibition of cell migration and invasion in both cell lines as well as inhibition of matrix metalloproteinase-2 activity and expression were detected. Importantly, the anticancer stemness and antimetastasis effects in each of these assays were greater for the combined treatment with SQE and CIS than with each treatment individually. In conclusion, the data suggest that SQE alone, or in combination with CIS, represents a promising therapeutic strategy for eliminating cancer stemness and cell invasion potential of CSCs, thereby treating and preventing metastatic lung cancer cells.

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“…and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-') starting on al., 1984;Dhingra et al, 1985; Kawahara et al, 1991). Treatment regimens in which one further active chemotherapeutic agent has been added to vinca alkaloid and cisplatin have been tried in an attempt to improve response and survival rates.…”

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“…Response rates of approximately 30% have since been shown in advanced NSCLC using a combination of VDS + CDDP (VP) (Elliott et al, 1984;Dhingra et al, 1985;Kawahara et al, 1991). Treatment regimens in which one further active chemotherapeutic agent has been added to vinca alkaloid and cisplatin have been tried in an attempt to improve response and survival rates.…”

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A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer

Nakano

Ikegami²,

Nakamura³

et al. 1996

Br J Cancer

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Summary Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m2 iv.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-') starting on al., 1984;Dhingra et al., 1985; Kawahara et al., 1991). Treatment regimens in which one further active chemotherapeutic agent has been added to vinca alkaloid and cisplatin have been tried in an attempt to improve response and survival rates. The combination of mitomycin with VP (MVP) has been reported to achieve response rates of 20-61% (Kris et al., 1986; Einhorn et al., 1986; Miller et al., 1986; Joss et al., 1990;Fukuoka et al., 1991). Although these intensive combination chemotherapy regimens achieve an improvement in objective response, serious drug-related toxicity is often experienced. Active chemotherapeutic regimens that are less toxic would therefore be desirable.Although 5-fluorouracil (5-FU) shows limited activity as a single agent in NSCLC, it reacts synergistically with CDDP against murine tumours (Schabel et al., 1979; Mabel and Little, 1979). This has prompted clinical studies of the combination of CDDP and 5-FU against NSCLC. Weiden et al. (1985) have reported a response rate of 37% in NSCLC using this combination. Continuous infusion (CI) of 5-FU has been found to increase the therapeutic response and decrease myelosuppression compared with the use of bolus injections (Seifert et al., 1975;Kish et al., 1985). Decker et al. (1983) found the combination of CDDP and a 5 day infusion of 5-FU useful in the treatment of head and neck cancers. They reported a 94% response rate, including a complete response rate of 63%. In a pilot study by the Mid-Atlantic Oncology Program, CDDP (120 mg m-2) infused over 24 h + CI 5-FU gave a response rate of 47% in advanced NSCLC (Heim et al., 1986). Toxicology profiles of these CDDP + 5-FU regimens indicate less haematological and nephrological toxicity than standard dose VP and MVP regimens. However, a higher incidence of severe mucositis was observed, and, if doxorubicin was also included, clinically significant myelosuppression, similar to that encountered with VP and MVP regimens, was also experienced (Ruckdeschel et al., 1981). Although improved response rates have been achieved, an optimum dose and schedule has yet to be identified.These reports encouraged us to perform a phase II trial of CDDP and VDS in combination with CI 5-FU against advanced NSCLC. We decided to administer VP separately from CI 5-FU, in an attempt to minimise toxicity without affecting efficacy. In most of the earlier studies CDDP and 5-FU were administered on the same day. The trial was designed so that CDDP + VDS and CI 5-FU were injected on alternate weeks. The immediate objectives were to determine the major objective response rate to this treatment programme, and to define the toxicities involved. The activity of this combination against advanced NSCLC has not been studied previously.Patients a...

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Randomized trial of three combinations of cisplatin with vindesine and/or VP-16-213 in the treatment of advanced non-small-cell lung cancer.

Cited by 73 publications

References 11 publications

A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer

A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer

Combination of Sasa quelpaertensis Nakai Leaf Extract and Cisplatin Suppresses the Cancer Stemness and Invasion of Human Lung Cancer Cells

A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer

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