|Year : 2021 | Volume
| Issue : 2 | Page : 71-75
Carboplatin in combination with 3-weekly paclitaxel as first-line therapy in patients with recurrent/metastatic head-and-neck cancers: A regional cancer center experience
Pooja Babbar1, AH Rudresha1, Lokanatha Dasappa1, Linu Abraham Jacob1, M C Suresh Babu1, KN Lokesh1, LK Rajeev1, Smitha Saldanha1, Vinay Kakkar2
1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
2 Department of Orthopaedics, Swami Dayanand Hospital, New Delhi, India
|Date of Submission||04-Apr-2021|
|Date of Decision||11-Jun-2021|
|Date of Acceptance||18-Jun-2021|
|Date of Web Publication||21-Aug-2021|
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Head-and-neck cancers (HNCs) collectively are the sixth most common malignancy diagnosed worldwide and treatment in recurrent/metastatic setting is challenging. This retrospective study aimed to evaluate the efficacy and tolerability of carboplatin and paclitaxel as first-line treatment in patients with recurrent and/or metastatic (R/M HNCs). Materials and Methods: A total of 182 patients with recurrent and/or metastatic HNC who received carboplatin and paclitaxel combination 3 weekly as first-line therapy at medical oncology department of our tertiary care cancer institute in Bangalore between January 2018 and January 2020 were reviewed. The patients who progressed during chemotherapy were receiving oral metronomic chemotherapy or best supportive chemotherapy. The patients were followed up every 2 monthly. Results: At the completion of treatment, the overall response rate was 15.4%. The median progression-free survival was 4.3 months (95% confidence interval [CI]: 2.9–5.6), and the median overall survival was 8.2 months (95% CI: 6.8–9.7). The main toxicities in the present study were Grade 3–4 hematologic 19.8%, mucositis 1.6%, and diarrhea 2.7%, and the rate of febrile neutropenia was 6.6%. None of the patients died of treatment-related toxicity. Conclusion: The combination of carboplatin with 3-weekly paclitaxel is effective in R/M HNC patients.
Keywords: Carboplatin, overall response rate, paclitaxel, recurrent/metastatic head-and-neck squamous cell carcinoma, survival
|How to cite this article:|
Babbar P, Rudresha A H, Dasappa L, Jacob LA, Babu M C, Lokesh K N, Rajeev L K, Saldanha S, Kakkar V. Carboplatin in combination with 3-weekly paclitaxel as first-line therapy in patients with recurrent/metastatic head-and-neck cancers: A regional cancer center experience. Oncol J India 2021;5:71-5
|How to cite this URL:|
Babbar P, Rudresha A H, Dasappa L, Jacob LA, Babu M C, Lokesh K N, Rajeev L K, Saldanha S, Kakkar V. Carboplatin in combination with 3-weekly paclitaxel as first-line therapy in patients with recurrent/metastatic head-and-neck cancers: A regional cancer center experience. Oncol J India [serial online] 2021 [cited 2023 Jun 5];5:71-5. Available from: https://www.ojionline.org/text.asp?2021/5/2/71/324230
| Introduction|| |
Head-and-neck cancers (HNCs) constitute a heterogeneous group of tumors which arise from the mucosal epithelium of the oral cavity, pharynx, and larynx, with variability in biologic behavior and outcomes. Worldwide, the HNCs form the sixth most common cancer and it is the most common cancer of males in India. Globally, it accounts to 4%–5% and in India to 30% of all cancers diagnosed. Worldwide of all the cancers, the number of new cases of HNCs diagnosed as per GLOBOCAN 2020 data is 9,31,931 with an estimated 4,67,125 deaths/year. India contributes 2,33,269 new cases of head-and-neck malignancies every year with an estimated 1,30,371 deaths/year. The mean age of patients at presentation of HNCs is the fifth and early sixth decades in Asian populations compared with the seventh and eighth decades in the North American population.,,
However, about two-thirds of head-and-neck squamous cell carcinoma (HNSSC) patients are diagnosed with locally advanced disease out of which despite primary treatment, more than a third of these patients have locoregional recurrences or distant metastases with a poor prognosis., Palliative treatment is considered as a treatment option for the majority of the recurrent/metastatic HNC patients. Treatment options include targeted therapies in combination with chemotherapy, combination or single-agent chemotherapy, oral metronomic chemotherapy, or best supportive care (BSC). Treatment choice is dependent on factors such as the performance status (PS) of the patient, comorbidity, symptoms, disease burden, prior treatment, patient preferences, and logistics.
For patients with recurrent or metastatic HNSCC (R/M HNSSC), the EXTREME regimen has been the standard of care in the first-line treatment for more than a decade. This regimen incorporates a platinum-based chemotherapy with cetuximab, followed by maintenance cetuximab, and it confers survival benefit and quality of life, with an overall response rate (ORR) of 36%, a median progression-free survival (PFS) of 5.6 months, and a median overall survival (OS) of 10.1 months, and a significant reduction in pain. However, the OS in R/M HNSSC patients hardly exceeds 1 year., Pêtre et al. showed that the weekly carboplatin and paclitaxel is a good option as first-line therapy for R/M HNSSC, mostly in patient's ineligible for cisplatin. Moreover, the regimens with carboplatin and paclitaxel did not seem to be much different from regimens with cisplatin and paclitaxel.
At our institution, paclitaxel and carboplatin given 3 weekly is the preferred regimen in patients ineligible for cisplatin or cetuximab: Due to various reasons including patient's choice and logistics.
With the above background, we retrospectively evaluated the efficacy and tolerability of carboplatin and paclitaxel as first-line treatment in patients with R/M HNSSC.
| Materials And Methods|| |
After obtaining the institutional ethical permission, we retrospectively reviewed the data of histologically confirmed R/M HNSCC patients who received carboplatin and paclitaxel 3-weekly combination as first-line therapy at medical oncology department of our tertiary care cancer institute in Bangalore, between January 2018 and January 2020. The Eastern Cooperative Oncology Group (ECOG) PS scoring system is a simple tool that is used in everyday practice to rate a patient's PS. Patients with the ECOG of 0–2 and at least unidimensional measurable lesion by imaging were included.
They were previously treated with single or multimodality treatment using surgery, radiotherapy, or previous chemotherapy administered for the treatment as either in the form of induction chemotherapy or in combination with radiation therapy either as part of definitive treatment or as adjuvant therapy.
Patients with concomitant malignancy, nasopharyngeal primary, or disease within 6 months of platinum-based curative intent treatment for localized disease were not considered. In addition, patients eligible for local therapy (surgery or re-irradiation) were excluded.
Pretreatment evaluation included a complete medical history, clinical examination, viral markers, complete blood count (CBC), complete biochemistry, cardiac evaluation with electrocardiogram, and two-dimensional ECHO as part of institution protocol. Imaging was done as a part of initial evaluation for the extent of the disease and for response assessment, and the diagnosis was confirmed by histologic examination of the biopsy.
The chemotherapy protocol consisted of paclitaxel, at a dose of 175 mg/m2 by a 3-h infusion followed by carboplatin at an area under curve (AUC = 5) every 3 weekly. All patients had received appropriate premedication and adequate hydration. Clinical examination, CBC, and biochemistry were assessed before each course of chemotherapy. The patients were evaluated for response assessment after the first three cycles and at the completion of six cycles of chemotherapy. Imaging was done to assess radiological response after three cycles and completion of six cycles of chemotherapy. All the scans pertinent for tumor response to chemotherapy or progression were reviewed.
A total of six cycles of palliative chemotherapy were administered based on response after three cycles. Patients were followed up clinically every 2 months after completion of six cycles of chemotherapy till the last date of follow-up. The toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events versions 4.03. In case of Grade III/IV toxicities, the drug dose was adjusted or stopped. A 25% dose reduction in subsequent cycles was done in patients developing any Grade IV or life-threatening toxicity. Dose reductions were done when granulocytopenia or thrombocytopenia persisted for >7 days or instances of a febrile neutropenia. Patients with the progressive disease (PD) were treated with either oral metronomic chemotherapy or BSC, depending on the patients' PS, disease extent, patients' choice, and logistics.
Response evaluation criteria in Solid Tumors 1.1 criteria was used to assess response to therapy in terms of complete response (CR), partial response (PR), stable disease (SD), and PD. Disease control rate (DCR) was defined as the combination of CR, PR, and SD. ORR was defined as the combination of CR and PR.
Duration of PFS was defined by the time from the treatment initiation until the documented recurrence or disease progression or death, and OS was calculated from the date of diagnosis until death. Kaplan–Meier survival analysis was used for the estimation of survival. All statistical analyses were performed using IBM SPSS Statistics for Windows, Version 23.0. (Armonk, NY: IBM Corp.).
| Results|| |
A total of 182 patients with R/M HNSSC received carboplatin and paclitaxel combination chemotherapy 3 weekly as first-line therapy during the study period. The baseline characteristics of the patient profile are mentioned in [Table 1]. The median age of patients at baseline was 49.00 ± 9.36 years within the range of 32–78 years and male-to-female ratio was 2.8. Most of the patients (58.7%) had an ECOG performance score of 1. The oral cavity was the most common site of tumor occurrence (37.9%), followed by the oropharynx (28.8%). Most patients had Stage IV disease (76.2%) at initial diagnosis. Majority of the patients (74.7%) had locoregional recurrent disease. Nearly 80% of patients received chemoradiation as part of initial treatment.
The radiological response rate after three cycles and after six cycles of chemotherapy, is presented in [Table 2]. After the first three cycles of chemotherapy, disease control was seen in 120 patients whereas 18 patients lost to evaluate response and 44 patients had PD. Hence, these 120 patients completed six cycles of planned chemotherapy.
|Table 2: Radiological response after three cycles and six cycles of chemotherapy|
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The ORR and DCR at the end of three cycles were 26.4% and 66.0% and after the completion of six cycles were 15.4% and 40.7%, respectively.
The median OS was 8.2 months (95% CI: 6.8–9.7), with a 1-year survival of 40.65% [Figure 1], and the median PFS was 4.3 months (95% CI: 2.9–5.6) [Figure 2].
None of the baseline patient and tumor characteristics were found to be significant determinant of survival by Cox multivariate analysis in recurrent and/or metastatic HNC patients.
Among patients progressed at the time of the last follow-up, 71.8% were started on oral metronomic chemotherapy and 28.2% patients considered for BSC.
The toxicities at the end of third cycle of chemotherapy are mentioned here. The rate of febrile neutropenia was 6.6% (n = 12). The rate of other Grade 3–4 toxicities was as follows: hematological toxicity – 19.8% (n = 36), mucositis – 1.6% (n = 3), and diarrhea – 2.7% (n = 5). Dose modification in the form of 25% reduction due to adverse events was reported in 15.3% (n = 28) of the patients. Growth factor was given as secondary prophylaxis in 24 patients. Alopecia was universal as expected. None of the patients died due to treatment-related complications.
| Discussion|| |
The clinical outcome of patients with R/M HNSCC remains dismal and hence maintaining quality of life during treatment is crucial. An ideal treatment extends survival while ensuring a good quality of life. This retrospective study evaluated the efficacy and tolerability of carboplatin and paclitaxel as first-line treatment in patients with R/M HNSSC. The chemotherapy protocol consisted of six cycles of paclitaxel at a dose of 175 mg/m2 by a 3-h infusion followed by carboplatin at an (AUC = 5) every 3 weekly. Several different regimens for paclitaxel plus carboplatin are commonly used and it has several advantages., Similar to our study, in a study by Ferrari et al., 27 patients were treated with a 3-weekly combination of paclitaxel 175 mg/m2 and carboplatin AUC 5 mg/ml/min for a maximum of four cycles. Clark et al. studied 37 patients with 200 mg/m2 by 3-h infusion of paclitaxel followed by carboplatin at AUC of 6 mg/mL/min through a 20–30-min infusion every 3 weeks.
In the present study, according to the assessment of response to carboplatin and paclitaxel as first-line chemotherapy 3 weekly after three cycles, SD was documented in 72 patients (39.56%), followed by a PR in 48 patients (26.37%) and disease progression in 44 patients (24.17%), giving a clinical benefit rate of 65.93%. Whereas, after six cycles of chemotherapy, the SD was recorded in 46 patients (25.27%), followed by PR in 28 patients (15.38%) and PD in 30 patients (16.48%), giving a clinical benefit rate of 40.65%. None of our patients achieved CR after three and six cycles of chemotherapy. These findings are correlating with previous studies. In a study by Ferrari et al., DCR was 51.8% (95% confidence interval [CI]: 32.0–71.3), whereas ORR was 25.9% (95% CI: 11.1–46). However, in Tahara et al. study, ORR, the primary end point, was 40%. Petre et al. conducted a retrospective analysis on efficay of first-line chemotherapy of carboplatin in combination with weekly paclitaxel in R/M HNSCC patients unfit to EXTREME schedule. They reported the ORR of 40%, CR of 4%, PR of 36%, SD of 28%, and PD of 14%.
Patients with recurrent or metastatic HNCs carry a poor prognosis with a median OS of 6–9 months and a median PFS of 2–4 months., In the current study, the median OS was 8.2 months (95% CI: 6.860–9.711), with a 1-year survival of 40.65%, and the median PFS was 4.3 months (95% CI: 2.9–5.6 months). These results are correlated with the study done by Ferrari et al. where the median OS was 8.0 months (range: 2–27), with a 1-year survival of 30.5%. The median PFS was 1.0 month (range: 0–14). Tahara et al. reported that the median OS was 14.7 months and PFS was 5.2 months. Pêtre et al. reported that the median OS for the entire population was 9.1 months (95% CI: 6.9–11.5) and the median PFS for all population was 4.7 months (95% CI: 3.7–5.2). Péron et al. used one of the chemotherapy regimens as carboplatin (AUC5/3 weeks) plus paclitaxel (80 mg/m2/week) in 69 patients. They found that the median OS of patients treated with a combination of carboplatin and paclitaxel was 10.5 (7.6–13.1) months.
The main toxicities (Grade 3–4) in the present study were hematologic in 19.7%, mucositis in 1.6%, and diarrhea in 2.7%, and the rate of febrile neutropenia was 6.5%. None of the patients died of treatment-related toxicity. In Péron et al. study, three patients died of febrile neutropenia after first-line carboplatin and paclitaxel combination. Stathopoulos et al. reported Grade 3–4 toxicity in 22.6% of patients. The toxicity profile in the present study was comparable with the previous studies which used traditional 3-weekly administration of carboplatin in combination with paclitaxel., The regimen used in this study was effective at a relative minor cost in terms of toxicity. This is a feasible regimen in terms of outcomes, tolerability, and patient logistics.
| Conclusion|| |
The study can be concluded that the combination of carboplatin with 3-weekly paclitaxel is effective and tolerable in patients suffering from R/M SCCHN. The results showed that this combination has significant activity, with the DCR of 40.7% in first-line treatment of R/M SCCHN. Toxicities were manageable and were tolerated in the outpatient clinic, with 3-weekly adjustments of dosages according to toxicity. Many patients are not eligible for cisplatin, and our study suggests that carboplatin with 3-weekly paclitaxel can be a good alternative for these unfit patients and even possibly for fit patients. Further evaluation of carboplatin in combination with 3-weekly paclitaxel in R/M HNCs is needed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al.
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49.
Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today
. [Last accessed 2021 Jun 04].
Agarwal AK, Sethi A, Sareen D, Dhingra S. Treatment delay in oral and oropharyngeal cancer in our population: The role of socio-economic factors and health-seeking behaviour. Indian J Otolaryngol Head Neck Surg 2011;63:145-50.
Diaz EM Jr., Holsinger FC, Zuniga ER, Roberts DB, Sorensen DM. Squamous cell carcinoma of the buccal mucosa: One institution's experience with 119 previously untreated patients. Head Neck 2003;25:267-73.
Lin CS, Jen YM, Cheng MF, Lin YS, Su WF, Hwang JM, et al.
Squamous cell carcinoma of the buccal mucosa: An aggressive cancer requiring multimodality treatment. Head Neck 2006;28:150-7.
Magnes T, Melchardt T, Weiss L, Mittermair C, Neureiter D, Klieser E, et al.
Prognostic score in patients with recurrent or metastatic carcinoma of the head and neck treated with cetuximab and chemotherapy. PLoS One 2017;12:e0180995.
Péron J, Ceruse P, Lavergne E, Buiret G, Pham BN, Chabaud S, et al.
Paclitaxel and cetuximab combination efficiency after the failure of a platinum-based chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Anticancer Drugs 2012;23:996-1001.
Taberna M, Oliva M, Mesia R. Cetuximab-containing combinations in locally advanced and recurrent or metastatic head and neck squamous cell carcinoma. Front Oncol 2019;9:383.
Sacco AG, Cohen EE. Current treatment options for recurrent or metastatic head and neck squamous cell carcinoma. J Clin Oncol 2015;33:3305-13.
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al.
Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116-27.
Pêtre A, Dalban C, Karabajakian A, Neidhardt EM, Roux PE, Poupart M, et al.
Carboplatin in combination with weekly Paclitaxel as first-line therapy in patients with recurrent/metastatic head and neck squamous cell carcinoma unfit to EXTREME schedule. Oncotarget 2018;9:22038-46.
Kies MS, Holsinger FC, Lee JJ, William WN Jr., Glisson BS, Lin HY, et al.
Induction chemotherapy and cetuximab for locally advanced squamous cell carcinoma of the head and neck: Results from a phase II prospective trial. J Clin Oncol 2010;28:8-14.
Wanebo HJ, Lee J, Burtness BA, Ridge JA, Ghebremichael M, Spencer SA, et al.
Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: A phase II ECOG-ACRIN trial (E2303). Ann Oncol 2014;25:2036-41.
Ferrari D, Fiore J, Codecà C, Di Maria G, Bozzoni S, Bordin V, et al
. A phase II study of carboplatin and paclitaxel for recurrent or metastatic head and neck cancer. Anticancer Drugs 2009;20:185-90.
Clark JI, Hofmeister C, Choudhury A, Matz G, Collins S, Bastian R, et al.
Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma. Cancer 2001;92:2334-40.
Tahara M, Kiyota N, Yokota T, Hasegawa Y, Muro K, Takahashi S, et al.
Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02). Ann Oncol 2018;29:1004-9.
Specenier PM, Vermorken JB. Recurrent head and neck cancer: Current treatment and future prospects. Expert Rev Anticancer Ther 2008;8:375-91.
Tsao AS. Novel therapies in metastatic head and neck squamous cell carcinoma. Community Oncol 2009;6:310-6.
Stathopoulos GP, Rigatos S, Papakostas P, Fountzilas G. Effectiveness of paclitaxel and carboplatin combination in heavily pretreated patients with head and neck cancers. Eur J Cancer 1997;33:1780-3.
[Figure 1], [Figure 2]
[Table 1], [Table 2]