Carboplatin/5-fluorouracil as an Alternative to Cisplatin/5-Fluorouracil for Metastatic and Recurrent Head and Neck Squamous Cell Carcinoma and Nasopharyngeal Carcinoma

Abstract

Background: Palliative chemotherapy with cisplatin/5-fluorouracil (5FU) is the commonest regimen employed for metastatic and recurrent head and neck squamous cell carcinoma (SCCHN) and nasopharyngeal carcinoma (NPC). However, this regimen is cumbersome requiring 5 days of admission to hospital. Carboplatin/5FU may be an alternative regimen without compromising survival and response rates. This study aimed to compare the efficacy and toxicity of carboplatin/5FU regimen with the cisplatin/5FU regimen. Materials and Methods: This retrospective study looked at patients who had palliative chemotherapy with either cisplatin/5FU or carboplatin/5FU for metastatic and recurrent SCCHN and NPC. It included patients who were treated at UKMMC from 1 st January 2004 to 31 st December 2009 with either palliative IV cispaltin 75 mg/m 2 D1 only plus IV 5FU 750 mg/m 2 D1-5 infusion or IV Carboplatin AUC 5 D1 only plus IV 5FU 500 mg/m 2 D1-2 infusion plus IV 5FU 500 mg/m 2 D1-2 bolus. The specific objectives were to determine the efficacy of palliative chemotherapy in terms of overall response rate (ORR), median progression free survival (PFS) and median overall survival (OS) and to evaluate the toxicities of both regimens. Results: A total of 41 patients were eligible for this study. There were 17 in the cisplatin/5FU arm and 24 in the carboplatin/5FU arm. The ORR was 17.7 % for cisplatin/5FU arm and 37.5 % for carboplatin/5FU arm (p-value=0.304). The median PFS was 7 months for cisplatin/5FU and 9 months for carboplatin/5FU (p-value=1.015). The median OS was 10 months for cisplatin/5FU arm and 12 months for carboplatin/5FU arm (p-value=0.110). There were 6 treatment-related deaths (6/41=14.6%), four in the carboplatin/5FU arm (4/24=16.7%) and 2 in the cisplatin/5FU arm (2/17=11.8%). Grade 3 and 4 hematologic toxicity was also more common with carboplatin/5FU group, this difference being predominantly due to grade 3-4 granulocytopenia (41.6% vs. 0), grade 3-4 anemia (37.5% vs. 0) and grade 3-4 thrombocytopenia (16.6% vs. 0). Conclusions: Carboplatin/5FU is not inferior to cisplatin/5FU with regard to its efficacy. However, there was a high rate of treatment-related deaths with both regimens. A better alternative needs to be considered.

Concurrent 5‐fluorouracil and carboplatin for the treatment of canine carcinomas

“…Seven additional dogs had NED; therefore, they were not included in the response evaluation. In humans, combination protocols with 5‐FU and platinum drugs have become the standard of care for patients with head and neck, nasopharyngeal and colorectal carcinomas . However, these protocols are not commonly utilized in veterinary medicine.…”

“…In humans, combination protocols with 5-FU and platinum drugs have become the standard of care for patients with head and neck, nasopharyngeal and colorectal carcinomas. [16][17][18][19][20] However, these protocols are not commonly utilized in veterinary medicine. Synergism is seen with this approach, likely due to inhibition of thymidylate synthase by fluorouracil, with resultant impaired DNA repair and subsequent DNA damage.…”

“…However, synergism with other chemotherapy agents, specifically platinum agents, [13][14][15] has resulted in greater clinical efficacy compared to single agent therapy, and is now standard of care in many human carcinomas including head and neck and gastrointestinal epithelial tumours. [16][17][18][19][20] This is likely due to fluorouracil's ability to decrease DNA repair and increase DNA damage via thymidylate synthase inhibition, 21,22 and downregulation of thymidylate synthase by platinum agents, specifically oxaliplatin. 23 Carboplatin is the main platinum agent used in veterinary oncology, due to its ease of administration and low rate of side effects, specifically nephrotoxicity and emesis.…”

A meta-analysis comparing cisplatin-based to carboplatin-based chemotherapy in moderate to advanced squamous cell carcinoma of head and neck (SCCHN).

“…The tolerability of the carboplatin-based regimen was better than that of the cisplatin-based regimen [10]. Currently, there have also been several other studies comparing the cisplatin-based regimen with the carboplatinbased regimen [11][12][13][14][15][16][17][18][19][20][21], but none of these studies were sufficiently large to demonstrate a statistically significant effect.…”

Selective Radiotherapy after Distant Metastasis of Nasopharyngeal Carcinoma Treated with Dose-Dense Cisplatin plus Fluorouracil

“…Chemotherapy is the main method for treating distant metastasis of NPC and various kinds of cytotoxic drugs have anticancer activity to NPC. Although there are many drugs in recent years, cisplatin is the most effective drug treatment for NPC now (Kua, et al, 2013). The response rate and progression-free survival time of cisplatin in combination with docetaxel or gemcitabine scheme was not superior to those of cisplatin in combination with fluorouracil (Kertmen et al, 2015).…”