Efficacy and Toxicity of Weekly Carboplatin and Paclitaxel as Induction or Palliative Treatment in Advanced Esophageal Cancer Patients

Abstract

Many patients have advanced esophageal cancer at diagnosis. However, the most optimal treatment has not been identified. Therefore, we evaluated a weekly regimen of carboplatin (area under the curve (AUC)) of 4 and paclitaxel at 100 mg/m2 as an induction or palliative treatment. All patients with advanced (gastro)esophageal cancer treated with this regimen between 2002–2018 were included. Exclusion criteria were previous radiotherapy or treatment elsewhere. Data on toxicity, response, and survival were collected. Analyses were performed in two groups: induction (iCT) or palliative chemotherapy (pCT). Median progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan–Meier method. A total of 291 patients was included (iCT: 122; pCT: 169). Most patients had T3 carcinoma (iCT: 54%; pCT: 66%) and stage IV disease (iCT: 42%; pCT: 91%). A toxicity grade ≥3 occurred mainly as hematological toxicity (iCT: 71%; pCT: 73%) and gastrointestinal toxicity (iCT: 3%; pCT: 5%). Response rates were 48% (iCT) and 44% (pCT). Esophagectomy or definitive chemoradiotherapy followed in 42% of iCT, resulting in a PFS of 22.1 months (interquartile range (IQR): 12.4–114.2) and OS of 26.8 months (IQR: 15.4–91.7). For pCT, PFS was 8.2 months (IQR: 5.1–14.5) and OS 10.9 months (IQR: 6.5–18.3). This retrospective cohort study demonstrated that weekly carboplatin (AUC4) and paclitaxel (100 mg/m2) is a well-tolerated and effective induction or palliative treatment regimen for patients with locally advanced or metastatic disease. Future research should directly compare this treatment regimen with other first-line treatment options to determine its true value for clinical practice.

Tissue Type Differences in ABCB1 Expression and Paclitaxel Tissue Pharmacokinetics in Patients With Esophageal Cancer

“…Patients, 18 years or older, were eligible if they were diagnosed with a histologically proven malignancy of the esophagus that was safely accessible by upper endoscopy. They were treated with weekly paclitaxel and carboplatin with or without concomitant radiotherapy in a standard regimen ( Supplementary Methods 1 ) ( Polee et al, 2004 ; van Hagen et al, 2012 ; de Man et al, 2019 ). Patients had to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.…”

“…Esophageal cancer is the 7th most common cause of cancer-related mortality worldwide ( Global Burden of Disease Cancer et al, 2018 ). Paclitaxel in combination with carboplatin and radiotherapy is highly effective in the curative setting of esophageal cancer, and in combination with carboplatin alone it has shown moderate efficacy both during induction chemotherapy and in the palliative setting of this tumor type ( Polee et al, 2004 ; van Hagen et al, 2012 ; Shapiro et al, 2015 ; de Man et al, 2019 ). Nonetheless, a substantial part of the patients with esophageal cancer do not benefit from this treatment or show progression of disease short after their treatment has stopped ( Chirieac et al, 2005 ; de Man et al, 2019 ; Toxopeus et al, 2019 ).…”

Can Cisplatin Therapy Be Improved? Pathways That Can Be Targeted

“…Carboplatin is approved for the treatment of ovarian and testicular cancers [12]. It is also widely used for treating head and neck [13], oesophageal [14], cervical, salivary gland, retinoblastoma [15] and glioblastoma cancers [16]. However, carboplatin is not beneficial for treating cisplatin-resistant tumours as the mechanisms of resistance for both drugs are similar.…”

DataSheet1.DOCX

“…Patients, 18 years or older, were eligible if they were diagnosed with a histologically proven malignancy of the esophagus that was safely accessible by upper endoscopy. They were treated with weekly paclitaxel and carboplatin with or without concomitant radiotherapy in a standard regimen (Supplementary Methods 1) (Polee et al, 2004;van Hagen et al, 2012;de Man et al, 2019). Patients had to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.…”

“…Esophageal cancer is the 7th most common cause of cancerrelated mortality worldwide (Global Burden of Disease Cancer et al, 2018). Paclitaxel in combination with carboplatin and radiotherapy is highly effective in the curative setting of esophageal cancer, and in combination with carboplatin alone it has shown moderate efficacy both during induction chemotherapy and in the palliative setting of this tumor type (Polee et al, 2004;van Hagen et al, 2012;Shapiro et al, 2015;de Man et al, 2019). Nonetheless, a substantial part of the patients with esophageal cancer do not benefit from this treatment or show progression of disease short after their treatment has stopped (Chirieac et al, 2005;de Man et al, 2019;Toxopeus et al, 2019).…”