The present study describes a case of a 60-year-old Japanese man who was histologically diagnosed with lung adenocarcinoma harboring L858R mutation of epidermal growth factor receptor. He was successfully treated with gefitinib, but eventually developed leptomeningeal carcinomatosis. He underwent ventriculoperitoneal shunting for hydrocephalus and received erlotinib in place of gefitinib with concurrent whole brain radiotherapy; this resulted in dramatic improvement in his symptoms and performance status from four to one and he survived for as long as 13.6 months after the initiation of erlotinib therapy. This multidisciplinary approach may be particularly useful in terms of increasing survival and improving quality of life.
Background
Nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) significantly improved overall survival in patients with metastatic pancreatic adenocarcinoma. Anti-tumor synergy between GEM and nab-PTX was recently demonstrated in a mouse model. We planned to assess the efficacy and safety of the combination of nab-PTX + GEM in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.
Methods
Patients with advanced NSCLC with progressive disease after platinum-based chemotherapy, an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and adequate kidney, liver and bone marrow function were eligible. Treatment consisted of nab-PTX (100 mg/m
2
) + GEM (1000 mg/m
2
) on days 1 and 8 of each 3-week cycle until progression disease or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).
Results
Of the 28 patients enrolled, all were evaluable for response and toxicity. The median age was 68 years (range 47–79), and 23 were male and 5 female. The histologic subtypes were: adenocarcinoma in 19 patients, and squamous cell carcinoma in 9 patients. Seventeen patients had ECOG PS 1 and 11 patients had PS 0. Twenty-four patients were second line and 4 patients were third line. The median number of cycles administered was 4 (range 1–10). The overall response rate was 17.9%. The disease control rate was 67.9%. The median progression-free survival was 3.1 months (95% confidence interval [CI] =1.6–4.1). Adverse events were generally tolerable except grade 3 interstitial pneumonia with in 4 patients (14.3%).
Conclusion
The efficacy of nab-PTX in combination with GEM in advanced second or third-line NSCLC patients was limited and the frequent occurrence of interstitial pneumonia was unacceptable.
Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors >4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC. Patients and Methods: Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m 2 , on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit. Results: Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4-83.7). Two-year RFS was 56.8% (95% CI, 29.7-76.9). Conclusion: The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.
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