Weekly docetaxel and concomitant boost radiotherapy for non-small cell lung cancer. A phase I/II dose escalation trial

Koukourakis, Michael I.; Kourousis, C.; Kamilaki, M.; Koukouraki, Sophia; Giatromanolaki, Alexandra; Kakolyris, Stylianos; Kotsakis, A.; Androulakis, N.; Bahlitzanakis, N; Georgoulias, V.

doi:10.1016/s0959-8049(97)10101-0

Cited by 63 publications

(36 citation statements)

References 20 publications

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“…It was also also reported that CRTx including docetaxel produced a response rate of 96% and a complete response rate of 50% in patients with head and neck cancer (16). These findings demonstrated that the combined use of docetaxel and radiation improved the tumor response, compared with docetaxel or radiation alone (17,18). Recent studies demonstrated the cell-killing effects of radiation and docetaxel on squamous cell carcinoma (SCC) cell lines in vitro, and also demonstrated the same effect on SCC cells in vivo (19)(20)(21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 68%

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Tabuchi

Ozawa

Koyanagi

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Esophageal squamous cell carcinoma (ESCC)is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0x10 -11 to 10 -7 M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC 50 for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0x10 -10 M; TE-2 and TE-3, ≤1.0x10 -9 M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity. This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.

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Section: Introductionmentioning

confidence: 68%

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Tabuchi

Ozawa

Koyanagi

et al. 2011

Experimental and Therapeutic Medicine

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“…The feasibility of concurrent treatment with single-agent docetaxel and radiotherapy for unresectable advanced NSCLC was established in a series of small phase I studies (Koukourakis et al, 1998;Mauer et al, 1998), and response rates of up to 80% have been reported in phase II trials in this setting (Kim and Khuri, 2002).…”

mentioning

confidence: 99%

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer

Scagliotti

Szczęsna²,

Ramlau³

et al. 2006

Br J Cancer

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This trial aimed to assess the feasibility and tumour control of concurrent chemoradiotherapy or radiotherapy alone after docetaxelbased induction chemotherapy in locally advanced non-small-cell lung cancer (NSCLC). Patients with stage IIIA/IIIB NSCLC received two 21-day cycles of induction chemotherapy with docetaxel (85 mg m À2 , day 1) plus cisplatin (40 mg m À2 , days 1 and 2). Patients without disease progression on day 43 were randomised to radiotherapy (2 Gy for 5 days week À1 ; total 60 Gy) alone or with docetaxel 20 mg m À2 once weekly every 6 weeks. Of 108 patients who received induction chemotherapy, 104 were evaluable for response. After induction chemotherapy, the overall response rate (ORR) was 44%; 91 (88%) patients had no disease progression and 89 were subsequently randomised to local treatment. After randomised therapy, the ORR was 53% (chemoradiotherapy 58%; radiotherapy 48%). Median survival and time to progression were 14.9 and 7.8 months, respectively, for chemoradiotherapy and 14.0 and 7.5 months, respectively, for radiotherapy. The most common toxicities during induction chemotherapy and randomised therapy were grades 3 -4 neutropenia and grade 3 lymphocytopenia, respectively. Docetaxel -cisplatin induction therapy followed by concurrent docetaxel and thoracic radiotherapy is a feasible treatment option, showing good clinical activity and tolerability, for locally advanced NSCLC.

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“…In previous phase I/II studies we established the MTD of each one of these drugs for combination with radiotherapy (Koukourakis et al, 1998a(Koukourakis et al, , 1999a. Mucosa toxicity was high and unnecessary splits of radiotherapy were enforced, which may have reduced the efficacy of the regimens (Koukourakis et al, 1999c).…”

Section: Discussionmentioning

confidence: 99%

“…The chemo -radiotherapy scheme used is diagrammatically reported in Table 1 72 every 2 weeks were the maximum tolerated doses identified in previously conducted chemo -radiotherapy dose escalation studies (Koukourakis et al, 1998a;1999b). No further escalation beyond this 'maximum dose level' was to be tried.…”

Section: Chemo -Radiotherapy Combination and Dose Escalationmentioning

confidence: 99%

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Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

et al. 2002

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The substantial augmentation of the radiation sequelae during chemo -radiotherapy with novel drugs masks the real potential of such regimens. In this study we examined whether subcutaneous administration of amifostine can reduce the toxicity of a highly aggressive chemo -radiotherapy scheme with Stealth Ò liposomal doxorubicin (Caelyx Ò ) and Docetaxel (Taxotere Ò ) in non-small cell lung cancer. Twenty-five patients with stage IIIb non-small cell lung cancer were recruited in a phase I/II dose escalation trial. The starting dose of Taxotere Ò was 20 mg m 72 week and of Caelyx Ò was 15 mg m 72 every two weeks, during conventionally fractionated radiotherapy (total dose of 64 Gy). The dose of Taxotere Ò /Caelyx Ò was, thereafter, increased to 20/25 (five patients) and 30/25 mg m 72 (15 patients). Amifostine 500 mg was given subcutaneously before each radiotherapy fraction, while an i.v. amifostine dose of 1000 mg preceded the infusion of docetaxel. The 'in-field' radiation toxicity was low. Grade 3 esophagitis occurred in 9 out of 25 (36%) patients. Apart from a marked reduction of the lymphocyte counts, the regimen was deprived from any haematological toxicity higher than grade 1. No other systemic toxicity was noted. The CR and CR/PR rates in 15 patients treated at the highest dose level was 40% (6 out of 15) and 87% (13 out of 15) respectively. It is concluded that the subcutaneous administration of amifostine during high dose Taxotere Ò / Caelyx Ò chemo -radiotherapy is a simple and effective way to render this aggressive regimen perfectly well tolerated, by reducing the systemic and the 'in-field' toxicity to the levels expected from simple conventional radiotherapy. The impressive tolerance and the high CR rate obtained encourages the conduct of a relevant randomized trial to assess an eventual survival benefit in patients with non-small cell lung cancer.

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Weekly docetaxel and concomitant boost radiotherapy for non-small cell lung cancer. A phase I/II dose escalation trial

Cited by 63 publications

References 20 publications

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines

Docetaxel-based induction therapy prior to radiotherapy with or without docetaxel for non-small-cell lung cancer

Concurrent administration of Docetaxel and Stealth® liposomal doxorubicin with radiotherapy in non-small cell lung cancer : excellent tolerance using subcutaneous amifostine for cytoprotection

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