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ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 1  |  Page : 70-73
 

Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?


1 Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
2 Division of Clinical Research and Biostatistics, Malabar Cancer Centre, Kannur, Kerala, India
3 Department of Radio Diagnosis, Tata Memorial Centre, Mumbai, Maharashtra, India
4 Department of Surgical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India

Date of Web Publication3-Feb-2016

Correspondence Address:
K Prabhash
Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.175604

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 » Abstract 

Background: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil) is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. Methods: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC) in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow-up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi-square analysis was done to compare response rates (RRs) between regimens. Results: Two hundred and forty-five patients were identified. The median age was 45 years (24–70 years), 208 (84.9%) were male patients, and 154 patients (62.9%) had primary in the Buccal mucosa. The regimens received were TPF 22 (9%), docetaxel + cisplatin 97 (39.6%), paclitaxel + cisplatin 89 (36.3%), docetaxel + carboplatin 16 (6.5%) and paclitaxel + carboplatin 21 (8.6%). The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%), 56 (22.9%), 145 (59.2%) and 40 (16.3%). The 3 drugs regimen (TPF) had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004). Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094). Conclusions: TPF has better RR than a 2 drugs taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers.


Keywords: 2 drugs regimen, 3 drugs regimen, induction chemotherapy, locally advanced oral cancers, response


How to cite this article:
Noronha V, Patil V, Joshi A, Muddu V, Bhattacharjee A, Juvekar S, Arya S, Chaturvedi P, Chaukar D, Pai P S, Dcruz A K, Prabhash K. Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?. Indian J Cancer 2015;52:70-3

How to cite this URL:
Noronha V, Patil V, Joshi A, Muddu V, Bhattacharjee A, Juvekar S, Arya S, Chaturvedi P, Chaukar D, Pai P S, Dcruz A K, Prabhash K. Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?. Indian J Cancer [serial online] 2015 [cited 2021 Dec 1];52:70-3. Available from: https://www.indianjcancer.com/text.asp?2015/52/1/70/175604



 » Introduction Top


A variety of induction chemotherapy (IC) regimens have been used in head and neck cancers.[1],[2],[3],[4],[5],[6],[7] However, at present TPF (docetaxel, cisplatin, 5 fluorouracil) chemotherapy regimen is considered standard. It has shown betterment in response rate (RR) and overall survival over 2 drugs regimen of cisplatin and 5 fluorouracil (5 FU).[1],[2]

The administration of TPF regimen in the developing world is difficult. Logistical issues like finances and chemotherapy bed availability for 5 FU administration hampers our ability to deliver TPF regimen in all our patients receiving IC. Tolerance issues like uncontrolled comorbidities advanced age or poor nutritional status further limits our ability to deliver TPF in our patients.[7] A study done at our center reported that severe malnutrition was seen in 24.3% of our locally advanced head and neck cancer patients.[8] In such scenarios, a common chemotherapy regimen that we resort to and which has been reported from various other centers in developing and developed world is the 2 drugs combination regimen which eliminates 5 FU and consists of a taxane and platinum.[4],[5],[6],[9],[10],[11],[12] Exciting RRs in various sites in head and neck cancers have been reported with this regimen.[4],[5],[6],[12] However, this regimen has never been prospectively compared to the current standard of care regimen TPF. Although the most commonly used and studied taxane is docetaxel, there are studies in which paclitaxel is the taxane in the combination.[4],[5],[6],[12] There is no data on whether docetaxel is superior to paclitaxel and should be the taxane of choice in head and neck cancers.

The most common reason for using IC in our oral cavity cancer patients is to achieve resectability.[9] Hence, the RR becomes a very important endpoint, as a higher RR correlates with more patients developing significant tumor shrinkage which often correlates with more patients rendered resectable. We did this analysis with the aim of comparing the RRs of IC between the 3 drugs regimen (TPF) and 2 drugs regimen (taxane + platinum) and when using the 2 drugs regimen, to compare the RR between paclitaxel and docetaxel based regimen.


 » Methods Top


Locally advanced oral cancers following discussion in tumor board warranting IC for technically unresectable tumors were seen in medical oncology outpatient department (OPD). These patients then depending upon logistics and tolerability were either offered 3 drugs regimen (TPF) or 2 drugs regimen of platinum and either paclitaxel or docetaxel. The choice between paclitaxel and docetaxel was mainly based on financial affordability. After completion of 2 cycles of IC, these patients underwent response assessment scans. Depending upon the response and Eastern Cooperative Oncology Group (ECOG) performance status, they were planned for either surgical treatment or nonsurgical treatment. Surgical treatment consisted of surgery followed by adjuvant chemoradiation. Nonsurgical treatment consisted of radical chemotherapy to radiotherapy (RT), radical RT, palliative RT or palliative intent chemotherapy.

All management related details were prospectively maintained for these patients in the Microsoft Excel database in head and neck medical oncology OPD. This database was searched with the following mentioned selection criteria, and patients' data were extracted.

Selection criteria

  • Patients who received IC between the period January 2010 and December 2012
  • Locally advanced oral cancers considered as technically unresectable
  • Baseline axial imaging done within 1 month of the start of IC
  • Response assessment axial imaging done within 2 weeks of completion of chemotherapy regimen
  • Patients who had gross clinical progression of the disease not warranting axial imaging for confirmation were included.


Exclusion criteria

  • Patients who received 2 drugs regimen for tolerability issues
  • Patients who had taken prior treatment
  • Patients who had defaulted after 1 cycle of chemotherapy for logistic issues.


In the patients, who fulfilled all the inclusion criteria and none of the exclusion criteria, the baseline demographic details, staging details, tumor details, IC details and response to IC details were extracted.

Statistical Package for the Social Sciences (SPSS, IBM, Newyork) version 16 was used for analysis. Chi-square test was done for comparison of responses. The planned comparisons of response were between 3 drugs regimen (TPF) versus 2 drugs regimen (taxane + platinum) and in patients receiving 2 drugs regimen between docetaxel platinum and paclitaxel platinum. Binary logistic regression analysis was done for multivariate analysis for predictors of response.


 » Results Top


Baseline details

Two hundred and forty-five patients were identified. The median age was 45 years (24–70 years). Majority of the patients had buccal mucosa primary (62.9%). The ECOG PS was 0–1 in 95.1% of patients. The regimens were TPF in 22 patients (9%), docetaxel + cisplatin 97 (39.6%), paclitaxel + cisplatin 89 (36.3%), docetaxel + carboplatin 16 (6.5%) and paclitaxel + carboplatin 21 (8.6%). The baseline demographic and tumor details are provided in [Table 1]. [Table 2] shows a comparison of important prognostic factors in oral cancers between the cohorts of patients receiving different drug regimens (3 drugs vs. 2 drugs). There was an imbalance between the 2 drugs and 3 drugs cohort with N3 stage been more common in 3 drugs regimen cohort (31.8% vs. 9.9%, P = 0.002). All other factors were well matched between the 2 cohorts. In the cohort of patients receiving 2 drugs regimens, the group of patients receiving paclitaxel was well matched with the group of patients receiving docetaxel [Table 3].
Table 1: Baseline demographic and tumor details according to the regimen received

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Table 2: Important prognostic differences between 3 drugs recipients and 2 drugs recipient's Chi-square test has been used for comparisons

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Table 3: Important prognostic differences between paclitaxel recipients and docetaxel recipients

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Response

The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%), 56 (22.9%), 145 (59.2%) and 40 (16.3%). The 3 drugs regimen (TPF) led to a 50% RR as compared to a 22% RR with the 2 drugs regimen (P = 0.004). When comparing the type of taxane used, docetaxel containing regimens had 30.3% RR as against 17.2% RR with paclitaxel containing regimens (P = 0.094). There was no statistically significant difference in RR between patients receiving carboplatin or cisplatin.

On binary logistic regression of all patients among the tested variables of age, sex, nutritional status, subsite, T4b stage, N3 stage, tobacco use, smoking status and regimen used, only the use of 3 drugs regimen was predictive of having a response (P = 0.006). The hazard ratio for having a response with 3 drugs regimen was 3.56 (95% confidence interval 1.45–8.68).


 » Discussion Top


Docetaxel, cisplatin, 5 fluorouracil chemotherapy is the most widely used IC regimen.[1], 2, [13],[14],[15] However, TPF is toxic, and tolerance of this regimen is questionable, especially in nutritionally compromised patients. TPF is associated with 1–2% mortality rate and nearly 20% of patients cannot complete even two cycles of TPF regimen.[14] This chemotherapy regimen requires 5 days continuous infusion of 5 FU, extensive monitoring, prophylactic granocyte-colony stimulating factor, prophylactic antibiotics and intensive supportive care.[16] Because of these issues and financial constraints, many patients in developing world end up receiving a 2 drugs chemotherapy regimen, incorporating taxane and platinum or a dose modified TPF regimen.[9],[17] At our center, we offer every patient the 3 drugs TPF regimen; however, due to logistic issues of unavailability of indoor beds for admission, long travelling distance between place of stay and hospital or due financial constraints, many patients opt for the 2 drugs taxane and platinum regimen. This provided us the opportunity to compare these combinations for the efficacy.

In our study, the TPF regimen was associated with a better RR of 50% as compared to a RR of 22% with 2 drugs regimens. This provides information that TPF regimen should not be preferably substituted till there is doubt about tolerability of TPF regimen, or further studies provide evidence to the contrary. We can appreciate from [Table 2] that all major important prognostic factors were well-matched between the 2 cohorts except N3 disease status. In fact, N3 disease was more in the TPF cohort (31.8% vs. 9.9% P = 0.002). Surprisingly in a reported study from Herman et al. the paclitaxel carboplatin IC chemotherapy had similar outcomes as compared to the TPF regimen.[4] A closer look at that study confirms that it included stages III-IV patients. In contrast, in our study only stage IV patients were included with 10% of patients having stage IVb status. In addition, the patient population in the Herman et al. study predominantly had a primary in the oropharynx.[4] A large proportion of oropharyngeal tumors have an association with human papillomavirus and hence these patients may not be ideal candidates for intensive chemotherapy regimens.[18],[19] All of the patients in our study had oral cavity primaries. It appears that the chemotherapy may have differential sensitivity for oral cavity as compared to the pharyngeal tumor.[11],[20] It appears that in oropharyngeal and laryngeal tumor sites chemotherapy may add more benefit than oral cavity cancers.[21]

There have been very few studies describing a 2 drugs taxane and platinum regimen as IC for head and neck cancer and those who have either used paclitaxel or docetaxel.[4],[5],[6],[12],[22] Probably ours is the only study so far, reporting a comparison of these two taxanes. Docetaxel with platinum was associated with a non significant increase in RR of 30.3% as opposed to 17.7% with paclitaxel and platinum. This suggests that perhaps 3 weekly paclitaxel may not be the best way of delivering paclitaxel, especially in the IC situation. The reported responses in 2 drugs regimens in our cohort of patients are much lower than those reported in other studies. However, our patients were a poor prognostic group of patients, including all oral cavity tumors, that were stage IV and technically unresectable, whereas in other studies discussing IC, oral cavity cancers were not predominant and stage III disease were included.[4],[5],[6],[12],[22] Its known that the response to IC decreases as stage of the disease increases.[23]

We would conclude by saying that such practice of giving 2 drugs chemotherapy (taxane and platinum) should only be done in patients not fit for TPF regimen. As far as possible 3 drugs regimen of TPF should be administered. If 2 drugs regimens have to be used for logistic issues, docetaxel seems to be a better agent than paclitaxel.

 
 » References Top

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Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357:1705-15.  Back to cited text no. 1
    
2.
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357:1695-704.  Back to cited text no. 2
    
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Argiris A, Heron DE, Smith RP, Kim S, Gibson MK, Lai SY, et al. Induction docetaxel, cisplatin, and cetuximab followed by concurrent radiotherapy, cisplatin, and cetuximab and maintenance cetuximab in patients with locally advanced head and neck cancer. J Clin Oncol 2010;28:5294-300.  Back to cited text no. 3
    
4.
Herman LC, Chen L, Garnett A, Feldman LE, Smith B, Weichselbaum RR, et al. Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer. Oral Oncol 2014;50:52-8.  Back to cited text no. 4
    
5.
Ready NE, Rathore R, Johnson TT, Nadeem A, Chougule P, Ruhl C, et al. Weekly paclitaxel and carboplatin induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck. Am J Clin Oncol 2012;35:6-12.  Back to cited text no. 5
    
6.
Pergolizzi S, Santacaterina A, Adamo B, Franchina T, Denaro N, Ferraro P, et al. Induction chemotherapy with paclitaxel and cisplatin to concurrent radiotherapy and weekly paclitaxel in the treatment of loco-regionally advanced, stage IV (M0), head and neck squamous cell carcinoma. Mature results of a prospective study. Radiat Oncol 2011;6:162.  Back to cited text no. 6
    
7.
Patil VM, Noronha V, Joshi A, Muddu VK, Dhumal S, Arya S, et al. Weekly chemotherapy as induction chemotherapy in locally advanced head and neck cancer for patients ineligible for 3 weekly maximum tolerable dose chemotherapy. Indian J Cancer 2014;51:20-4.  Back to cited text no. 7
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Rath S, Patil VM, Noronha V, Joshi A, Bhosale B, Punatar S, et al. Epidemiology of oral cancers referred for NACT, the demographics, clinical profile, and organ functions. J Clin Oncol 2013;31 Suppl; abstr e12520. Available from: http://www.meetinglibrary.asco.org/content/116116-132 [Last accessed on 2014 July 10].  Back to cited text no. 8
    
9.
Patil VM, Noronha V, Joshi A, Muddu VK, Gulia S, Bhosale B, et al. Induction chemotherapy in technically unresectable locally advanced oral cavity cancers: Does it make a difference? Indian J Cancer 2013;50:1-8.  Back to cited text no. 9
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Joshi A, Patil VM, Noronha V, Juvekar S, Deshmukh A, Chatturvedi P, et al. Is there a role of induction chemotherapy followed by resection in T4b oral cavity cancers? Indian J Cancer 2013;50:349-55.  Back to cited text no. 10
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11.
Joshi P, Patil V, Joshi A, Norohna V, Chaturvedi P, Chaukar D, et al. Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma. Indian J Cancer 2013;50:25-30.  Back to cited text no. 11
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Semrau S, Waldfahrer F, Lell M, Linke R, Klautke G, Kuwert T, et al. Feasibility, toxicity, and efficacy of short induction chemotherapy of docetaxel plus cisplatin or carboplatin (TP) followed by concurrent chemoradio-therapy for organ preservation in advanced cancer of the hypopharynx, larynx, and base of tongue. Early results. Strahlenther Onkol 2011;187:15-22.  Back to cited text no. 12
    
13.
Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): A randomised phase 3 trial. Lancet Oncol 2013;14:257-64.  Back to cited text no. 13
    
14.
Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, et al. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol 2014;32:2735-43.  Back to cited text no. 14
    
15.
Hitt R, Grau JJ, López-Pousa A, Berrocal A, García-Girón C, Irigoyen A, et al. A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 2014;25:216-25.  Back to cited text no. 15
    
16.
Patil VM, Chakraborty S, Shenoy PK, Manuprasad A, Sajith Babu TP, Shivkumar T, et al. Tolerance and toxicity of neoadjuvant docetaxel, cisplatin and 5 fluorouracil regimen in technically unresectable oral cancer in resource limited rural based tertiary cancer center. Indian J Cancer 2014;51:69-72.  Back to cited text no. 16
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Somani N, Goyal S, Pasricha R, Khuteta N, Agarwal P, Garg AK, et al. Sequential therapy (triple drug-based induction chemotherapy followed by concurrent chemoradiotherapy) in locally advanced inoperable head and neck cancer patients-Single institute experience. Indian J Med Paediatr Oncol 2011;32:86-91.  Back to cited text no. 17
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Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: A virus-related cancer epidemic. Lancet Oncol 2010;11:781-9.  Back to cited text no. 18
    
19.
Ang KK, Sturgis EM. Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma. Semin Radiat Oncol 2012;22:128-42.  Back to cited text no. 19
    
20.
Patil VM, Prabhash K, Noronha V, Joshi A, Muddu V, Dhumal S, et al. Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers. Oral Oncol 2014;50:1000-4.  Back to cited text no. 20
    
21.
Blanchard P, Baujat B, Holostenco V, Bourredjem A, Baey C, Bourhis J, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour site. Radiother Oncol 2011;100:33-40.  Back to cited text no. 21
    
22.
Huang CE, Lu CH, Chen PT, Chan CH, Chen WC, Wang WH, et al. Efficacy and safety of dose-modified docetaxel plus cisplatin-based induction chemotherapy in Asian patients with locally advanced head and neck cancer. J Clin Pharm Ther 2012;37:342-7.  Back to cited text no. 22
    
23.
Licitra L, Grandi C, Guzzo M, Mariani L, Lo Vullo S, Valvo F, et al. Primary chemotherapy in resectable oral cavity squamous cell cancer: A randomized controlled trial. J Clin Oncol 2003;21:327-33.  Back to cited text no. 23
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]

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