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Chemoradiotherapy in head neck cancer: induction chemotherapy ?
- Gabriela Studer, Christoph Glanzmann (11 May 2009)
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Gabriela Studer, Radiation Oncologist University Hospital Zurich, Department of Radiation Oncology, Raemistrasse 100, 8091 Zurich, Switzer, Christoph Glanzmann
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We like to comment on this most recent article by Posner and colleagues on induction chemotherapy (IC) in 166 larynx and hypopharynx cancer (LHC) [1], a subgroup out of the TAX 324 study [2]. This trial clearly showed the superiority of IC docetaxel plus cisplatin plus fluorouracil (TPF) over PF alone followed by radiotherapy with concomitant carboplatin. However, the following points are noticeable: focusing on the superior TPF arm of the study, there is still considerably low disease control, with progression free, laryngectomy free and overall survival rates of only 44%, 52% and 57% at 3 years, respectively. Reasons may be multi-factorial: first, there is no high grade evidence of the equivalence of concomitant carboplatin and cisplatin. In most studies using carboplatin, fluorouracil was added - the only study using concomitant carboplatin alone was a subgroup of a trial by Jeremic et al [3]. Furthermore, the radiation schedule with 5 fractions of 2.0Gy per week, applied with conventional (non-IMRT) techniques, may not be the most efficient regimen [Trial RTOG 0522]. The drop out rate of 20% during TPF IC, mainly due to disease progression and treatment related side effects (27% during the entire treatment), as described in the initial article on the TAX 324 trial [2], is higher than in other trials (<5%) [3-8]. In addition, a comparatively high rate of 29% in the TPF arm (even 65% in the PF arm) experienced treatment delay [3-8]. We know that gaps during radiation therapy and also long gaps between operation and postoperative radiation are associated with a loss of tumor control; this could also be the case for extended treatment time after start of IC. All these unfavourable components taken together, suboptimal outcome may result. In comparison, outcome in the own cohort of 123 LHC patients treated with primary radiochemotherapy using IMRT and concomitant weekly cisplatin chemotherapy (40mg/m2/week, in most patients) is higher, and there was no drop out of patients and no treatment related death (submitted): 3 year survival rates reached for progression free, laryngectomy free and overall survival were 71%, 85% and 80%, respectively (approximately 30% higher than in the superior TPF arm). With respect to the incidence of distant metastases, there was no difference between the two IC study arms, with 6% vs 7% following TPF vs PF, respectively. In the own IMRT cohort (~70% 4-7 cycles, 9% 1-3 cycles concomitant cisplatin, 5% concomitant erbitux without cisplatin, 16% of all patients underwent no systemic treatment), the rate of distant metastasis is identical with 7% [9]. Based on these facts, in only a small minority of all patients referred to our department, IC is considered to be indicated. Up to now, including this paper, there is yet no high level evidence for the superiority of IC over current standard radio-chemotherapy alone. We consider the conclusion, that TPF followed by carboplatin chemo- radiotherapy is a treatment option to improve survival in locally advanced LHC [1], premature. Results of ongoing prospective randomized studies on taxane-containing IC vs radio-chemotherapy alone (University of Chicago, SWOG/ECOG, Dana-Farber Cancer Institute, ASCO 2006 abstract 5515) should be awaited – those IC trials will hopefully reveal the answer to this important question. Considering the low risk of distant metastases in the own cohort of >700 IMRT patients, IC for reduction of distant metastases will be indicated only for a small subgroup. Only if IC will show also a substantial advantage for local control, it will be indicated for larger groups. References 1. Posner MR, Norris CM, Wirth LJ et al for the TAX 324 Study Group. Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival,surgery, and organ preservation. Annals of Oncology 2009; 20: 921–927. 2. Posner MR, Hershock DM, Blajman CRet al; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007; 357(17): 1705-15- 3. Jeremic B, Shibamoto Y, Stanisavljevic B et al: Radiation therapy alone or with concurrent low-dose daily either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck: A prospective randomized trial. Radiother Oncol 1997; 43:29-37. 4. Huguenin P, Beer KT, Allal A et al. Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy. J Clin Oncol. 2004; 22(23): 4665-73. 5. Budach V, Stuschke M, Budach W, et al. Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: Final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 prospective randomized trial. J Clin Oncol 2005; 23:1125- 1135. 6. Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003; 349: 2091-2098. 7. Calais G, Alfonsi M, Bardet E, et al. Randomized study comparing radiation alone RT versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 1999; 91: 2081 -2086. 8. Brizel DM, Albers MA, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998; 328: 1798-1804. 9. Studer G, Seifert B, Glanzmann C. Prediction of distant metastasis in head neck cancer patients: implications for induction chemotherapy and pre -treatment staging? Strahlenther Onkol. 2008; 184(11): 580-585. Gabriela Studer and Christoph Glanzmann Conflict of Interest:None declared |
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