A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non–small-cell lung cancer (a Vanderbilt cancer center affiliate network study)

Choy, Hak; DeVore, Ronald A.; Hande, Kenneth R.; Porter, Lester; Rosenblatt, Paul; Yunus, Furhan; Schlabach, Larry; Smith, C L; Shyr, Yu; Johnson, David H.

doi:10.1016/s0360-3016(00)00420-x

Cited by 88 publications

(52 citation statements)

References 33 publications

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“…However, with the exception of those regimens where concurrent chemotherapy consisted of single-agent cisplatin, most regimens using combination chemotherapy or third-generation agents concurrently with thoracic irradiation have shown severe additive toxicity, particularly oesophagitis and pneumonitis (Lee et al, 1996;Reckzeh et al, 1996;Frasci et al, 1997). Recently, there have been a number of attempts to further improve the results of combined chemoradiation by using more recently developed chemotherapy regimens and by adding sequential chemotherapy to concurrent chemoradiation in order to take possible advantage of two different chemoradiation strategies combined together (Greco et al, 1996;Choy et al, 1997;Isokangas et al, 1998). Although preliminary results have been extremely promising in terms of activity, the enhanced normal-tissue toxicity resulting from these novel chemoradiation regimens is worrying.…”

Section: Discussionmentioning

confidence: 99%

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Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer

et al. 1999

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Both induction chemotherapy and concurrent low-dose cisplatin have been shown to improve results of thoracic irradiation in the treatment of locally advanced non-small-cell lung cancer (NSCLC). This phase II study was designed to investigate activity and feasibility of a novel chemoradiation regimen consisting of induction chemotherapy followed by standard radiotherapy and concurrent daily low-dose cisplatin. Previously untreated patients with histologically/cytologically proven unresectable stage IIIA/B NSCLC were eligible. Induction chemotherapy consisted of vinblastine 5 mg m −2 intravenously (i.v.) on days 1, 8, 15, 22 and 29, and cisplatin 100 mg m −2 i.v. on days 1 and 22 followed by continuous radiotherapy (60 Gy in 30 fractions) given concurrently with daily cisplatin at a dose of 5 mg m −2 i.v. Thirty-two patients were enrolled. Major toxicity during induction chemotherapy was haematological: grade III–IV leukopenia was observed in 31% and grade II anaemia in 16% of the patients. The most common severe toxicity during concurrent chemoradiation consisted of grade III leukopenia (21% of the patients); grade III oesophagitis occurred in only two patients and pulmonary toxicity in one patient who died of this complication. Eighteen of 32 patients (56%, 95% CI 38–73%) had a major response (11 partial response, seven complete response). With a median follow-up of 38.4 months, the median survival was 12.5 months and the actuarial survival rates at 1, 2 and 3 years were 52%, 26% and 19% respectively. The median event-free survival was 8.3 months with a probability of 40%, 23% and 20% at 1, 2 and 3 years respectively. Induction chemotherapy followed by concurrent daily low-dose cisplatin and thoracic irradiation, in patients with locally advanced NSCLC, is active and feasible with minimal non-haematological toxicity. Long-term survival results are promising and appear to be similar to those of more toxic chemoradiation regimens, warranting further testing of this novel chemoradiation strategy. © 1999 Cancer Research Campaign

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Section: Discussionmentioning

confidence: 99%

“…New strategies to further improve local control, such as the addition of post-treatment radical surgery (Eberhardt et al, 1998) or the use of hyperfractionated radiotherapy (Choy et al, 1997;Frasci et al, 1997) should also be pursued.…”

Section: Discussionmentioning

confidence: 99%

Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer

et al. 1999

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“…120,121 For patients with locally advanced unresectable nonsmall cell lung carcinoma, combined treatment of paclitaxel with radiation has demonstrated an improved response rate. 122 The cells in the G 2 /M phase of the cell cycle are known to be the most sensitive to ionizing radiation, 120 explaining the radiosensitization of cancer cells by paclitaxel. On the other hand, the greatest augmentation of radiation response is noted not to be at the time of highest mitotic arrest, but rather 1 day after paclitaxel treatment, 123 suggesting an involvement of other mechanisms, such as reoxygenation of hypoxic tumor cells.…”

Section: Enhancement Of Paclitaxel-induced Apoptosis By Adjuvant Treamentioning

confidence: 99%

Paclitaxel-induced cell death

Wang

Soong

2000

Cancer

558

185

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“…In five phase II studies, the combination of paclitaxel and carboplatin was given weekly with concurrent radiotherapy, followed by two or four 21-day cycles of consolidation chemotherapy (Choy et al, 1998(Choy et al, , 2000Lau et al, 2001;Ratanatharathorn et al, 2001;Kaplan et al, 2004). The overall response rate varied from 71 to 79%.…”

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confidence: 99%

Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study

et al. 2006

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This study was performed to assess the efficacy and safety of preoperative chemoradiation consisting of carboplatin and paclitaxel and concurrent radiotherapy for patients with resectable (T2-3N0-1M0) oesophageal cancer. Treatment consisted of paclitaxel 50 mg m À2 and carboplatin AUC ¼ 2 on days 1, 8, 15, 22 and 29 and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by oesophagectomy. All 54 entered patients completed the chemoradiation without delay or dose-reduction. Grade 3 -4 toxicities were: neutropaenia 15%, thrombocytopaenia 2%, and oesophagitis 7.5%. After completion of the chemoradiotherapy 63% had a major endoscopical response. Fifty-two patients (96%) underwent a resection. The postoperative mortality rate was 7.7%. All patients had an R0-resection. The pathological complete response rate was 25%, and an additional 36.5% had less than 10% vital residual tumour cells. At a median follow-up of 23.2 months, the median survival time has not yet been reached. The probability of disease-free survival after 30 months was 60%. In conclusion, weekly neoadjuvant paclitaxel and carboplatin with concurrent radiotherapy is a very tolerable regimen and can be given on an outpatient basis. It achieves considerable down staging and a subsequent 100% radical resection rate in this series. A phase III trial with this regimen is now ongoing.

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A phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non–small-cell lung cancer (a Vanderbilt cancer center affiliate network study)

Cited by 88 publications

References 33 publications

Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer

Induction chemotherapy followed by concurrent standard radiotherapy and daily low-dose cisplatin in locally advanced non-small-cell lung cancer

Paclitaxel-induced cell death

Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study

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