Department of Radiotherapy, Institute of Postgraduate Medical Education and Research, Kolkata, India

Aim: One of the cancers that occurs most frequently worldwide is head and neck cancer. Oral cavity and pharynx cancers are the most frequent head and neck malignancies in India. Most of these tumors are in stage III or IV when they first manifest. The two main therapeutic techniques are surgery and radiation therapy. In order to improve local control, which leads to improved survival, concurrent chemoradiation is being researched. In light of the foregoing, we have begun this prospective, randomised experiment to determine the dosage, schedule, and order of therapy and to determine whether vinorelbine, when used as a radiosensitizer, is as effective as cisplatin in terms of compliance, local control, and toxicity.

Two arms were randomly assigned to each of 40 patients with advanced head and neck cancer. Weekly injections of 40mg/m2 of cisplatin were given to arm A in addition to radiotherapy. Along with radiotherapy, Arm B also received a weekly dose of vinorelbine (6 mg/m2). In a telecobalt machine, radiotherapy was administered at a dose of 6,600–7,000 Gy in traditional fractionation.

In advanced head and neck cancer, concurrent chemoradiation with vinorelbine led to a higher rate of CR than concurrent chemoradiation with cisplatin. The Cisplatin arm had greater toxicities, but they were tolerable. Vinorelbine can be suggested as a radiosensitizer in advanced head and neck cancer, even though Cisplatin was used as the radiosensitizer for the majority of the trial.

Keywords: vinorelbine, radiosensitizer, and concurrent chemoradiotherapy

Head and neck danger is the one of the most usually happening threat in India. The general male to female proportion is almost 4:1. It for the most part happens in the fifth 10 years or more. The guess of head and neck malignant growth relies upon the essential site, grade and physical degree of the illness. Beginning phase head and neck diseases can be relieved with a medical procedure or potentially radiotherapy however, for cutting edge arranges, the neighborhood disappointment rate in some cases drew closer as high as half. To work on the outcomes, joined methodology treatment with chemotherapy has been explored. The three ways to deal with the utilization of essential chemotherapy are neoadjuvant chemotherapy,[1-3] adjuvant chemotherapy and corresponding chemoradiotherapy. Corresponding chemoradiation is being explored with the objectives of further developed nearby control converting into further developed endurance, decrease of far off metastasis and conservation of organ capability.

The motivation behind managing chemotherapy and radiotherapy is to exploit the radiosensitizing capacity of large numbers of the dynamic medications for this illness and impact a sufficiently significant expansion in locoregional control, which would mean expanded survival.[4] Patients who got attending chemoradiotherapy had insignificantly further developed paces of locoregional control and illness free endurance. This was noticed fundamentally in patients with oropharyngeal cancer[5] when contrasted with different malignant growths. The medications generally ordinarily utilized as a component of a radiation joined approach are Cisplatin, 5FU and hydoxyurea. Cisplatin has far reaching use in consolidated methodology therapy in lung cancers[6] and head and neck cancers.[7] As of late, Vinorelbine[8-11] was utilized as a radiosensitizer. A larger part of the examinations was performed involving Cisplatin[12,13] as a radiosensitizer, albeit a few investigations likewise support utilization of Vinorelbine as a radiosensitizer.

This study was done in the radiotherapy branch of I.P.G.M.E.R, Kolkata, from September 2004 to July 2005. Forty patients of head and neck disease were randomized into two arms, with 20 patients in each arm.Patients of head and neck carcinoma having stage II-IV illness with squamous cell histology were remembered for this preliminary. These patients had no earlier medical procedure, chemotherapy or radiotherapy.

The exhibition status was >70% (as indicated by Karnofsky's scale). Hematological boundaries were inside the ordinary reach, similar to hemoglobin >11 mg%, outright neutrophil count >1,900, platelet count >1 lakh/mm3, serum bilirubin 1 mg%, liver chemicals inside 1.5-seasons of as far as possible and serum creatinine 1.5 mg%. Patients were barred from the review in the event that they had proactively gotten some type of anticancer treatment, on the off chance that there was presence of metastatic sickness, assuming they had partaken in a clinical preliminary over the most recent 30 days, assuming there was synchronous support in a clinical preliminary or on the other hand in the event that they had any wild fundamental disease like diabetes, tuberculosis and hypertensio.

Patients who satisfied the above qualification rules were expected to sign the educated assent structure and were then randomized to relegate both of the treatment arms.

Arm A: Outer pillar radiotherapy (EBRT) alongside week after week infusion Cisplatin 40 mg/m2 IV.

Arm B: EBRT alongside week after week Vinorelbine 6 mg/m2 IV.

The portion of EBRT was 66-70 Gy, with ordinary fractionation, utilizing a telecobalt machine with rope saving after 4,400 cGy.

Reaction was evaluated by neighborhood assessment and backhanded laryngoscopy multi month after fulfillment of radiotherapy. Customary follow-up was done at month to month spans. Neighborhood control was recorded utilizing the phrasing total reaction (CR), halfway reaction (PR) and moderate sickness (PD) (according to WHO definition).

Harmfulness evaluation was done week after week during therapy and from that point month to month as long as 90 days for intense poison levels utilizing Radiation Treatment Oncology Gathering standards. In this way, patients were being followed-up month to month as long as a half year and afterward at 3-month to month stretches for any indication of repeat and treatment-related horribleness.

Restorative methodology in head and neck disease is broadly examined and is a begging to be proven wrong one likewise, with the ideal treatment methodology, the aim of treatment and overseeing poison levels consuming the psyche of the doctor with the endurance impact characterizing the effectivity of treatment methodology.The administration of essential malignant growth is thought about independently for each anatomic site. On the off chance that outer bar radiation treatment is chosen, it could be given with either traditional once-everyday fractionation to 66-70 Gy in 2 Gy/division, 5 days seven days in a constant course or with a changed fractionation plan. EBRT may likewise be conveyed with power balanced radiation treatment (IMRT)[14] to decrease the portion to the ordinary tissues.[15]

The weaknesses of IMRT are that it is significantly more tedious to plan and treat the patient, the portion dissemination is frequently less homogeneous so that "problem areas" may build the gamble of late confusion and the gamble of minor miss might be expanded. Whether a modified fractionation plan is superior to a regular one relies upon the changed fractionation method that is chosen. Adjusted fractionation plans displayed to result in improved locoregional control rates are the College of Florida hyperfractionation procedure and HD Anderson attending support method. The Randomized Radiation Treatment Oncology Gathering 90-03 observed that intense poisonousness is expanded with modified fractionation though late harmfulness is equivalent with that of traditional fractionation.

The primary site's management is directly related to the neck's management. The justification for combining radiation and chemotherapy at the dosages specified was: a.to boost the responder and locoregional control rate for this rather advanced disease b.establishing the dose's acceptability in normal tissues in order to prevent harmful effects while simultaneously assessing the tolerability of the patients c.Acting on systemic micrometastasis, which was present at the diagnosis in more than 50% of cases, will lower the rates of distant metastasis.

Calais et al,[16] as of late detailed that illness free endurance and 3-year pace of locoregional control were fundamentally improved with accompanying chemotherapy, in spite of the fact that patients in the joined radiation treatment chemotherapy arm experienced higher paces of grade 3 or 4 mucositis, taking care of cylinder arrangement and serious cervical fibrosis.

Albeit a larger part of studies were performed by involving Cisplatin as the radiosensitizing drug, a few examinations likewise support the utilization of Vinorelbine as a radiosensitizer.

Following 1-year follow-up, CR is higher in the Vinorelbine in addition to radiation arm followed by the Cisplatin in addition to radiation arm, which needs further assessment. Despite the fact that poison levels like mucosal, hematologic and dermatologic were higher in they associative arm, they were sensible. All poison levels were fundamentally higher when Cisplatin was utilized as a radiosensitizer. Consistence was likewise more noteworthy with Vinorelbine as poison levels were less when contrasted and Cisplatin.

Our review had a set number of patients and the term of follow-up is likewise short. Further assessment of treatment convention with enormous number of patients and furthermore with delayed follow-up may decidedly affect endurance as the reaction rate is as of now showing improvement in a corresponding convention.

1. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, et al. Chemoradiotherapy vs radiotherapy in patients with advanced nasopharyngeal cancer: Phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16:1310–7. [PubMed] [Google Scholar]

2. Taylor SG, 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, et al. Randomized comparison of neoadjuvant cisplatin and flurouracil infusion followed by radiation vs. concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994;12:385–95. [PubMed] [Google Scholar]

3. Coughlin CT, Richmond RC. Biologic and clinical developments of cisplatin combined with radiation: Concepts, utility, projections for new trials, and the emergence of carboplatin. Semin Oncol. 1989;16:31–43. [PubMed] [Google Scholar]

4. Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet. 2000;355:949–55. [PubMed] [Google Scholar]

5. Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, Schroeder M, et al. Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001;50:1161–71. [PubMed] [Google Scholar]

6. Tannock IF. Combined modality treatment with radiotherapy and chemotherapy. Radiother Oncol completed. 1989;16:83–101. [PubMed] [Google Scholar]

7. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Eng J Med. 1991;324:1685–90. [PubMed] [Google Scholar]

8. Potier P. The synthesis of Navelbine prototype of a new series of vinblastine derivatives. Semin Oncol. 1989;16:2–4. [PubMed] [Google Scholar]

9. Mastbergen SC, Duivenvoorden I, Versteegh RT, Geldof AA. Cell cycle arrest and clonogenic tumor cell kill by divergent chemotherapeutic drugs Anticancer Res. 2000;20:1833–8. [PubMed] [Google Scholar]

10. Sudarshan G, Mahadev S. Vinorelbine as radiosensitizer in head and neck and oesophageal cancer: A plot study. Journal of Clinical Oncology, 2004 Asco Annual meeting proceedings (post meeting edition) (July 15 supplement) 2004;22:5562. [Google Scholar]

11. Grenman RA, Erjala KO, Pulkkiner JO, Kulmala JA, Alanen KA, Granma SE. Vinorelbine and concomitant irradiation in head and neck squamous cell cancer 2002 ASCO Annual Meeting Head and Neck Cancer: No. :257–7. [Google Scholar]

12. Gasparini G, Pozza F, Recher G, Panizzoni GA, Cristoferi V, Squaquara R, et al. Simultaneous cis-platinum and radiotherapy in inoperable or locally advanced squamous cell carcinoma of the head and neck. Oncology. 1991;48:270–6. [PubMed] [Google Scholar]

13. Glaser MG, Leslie MD, O’Reilly SM, Cheesman AD, Newlands ES. Weekly cisplatinum concomitant with radical radiotherapy in the treatment of advanced head and neck cancer. Clin Oncol (R Coll Radiol) 1993;5:286–9. [PubMed] [Google Scholar]

14. Chao CK, Ozyigit G, Tran BN. Pattern of failure in patients receiving definitive and post operative IMRT for head and neck cancer. Int J Radiat Oncol Biol Phys. 2003;15:312. [PubMed] [Google Scholar]

15. Adelstein DJ, Li Y, Adams GL, Wagner H, Jr, Kish JA, Ensley JF, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemo-radiotherapy in patients with unresectable squamous cell head and nack cancer. J Clin Oncol. 2003;21:92–8. [PubMed] [Google Scholar]

16. Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P, et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiotherapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst. 1999;91:2081–6. [PubMed] [Google Scholar]

Soumita Poddar . Vinorelbine and cisplatin compared in concurrent chemoradiotherapy for head and neck cancer. World Journal Of Hematology And Oncology 2022.