ABSTRACT
INTRODUCTION: Previous small-molecule antiangiogenics have compromised chemotherapy dose intensity in breast cancer. We present a phase I trial of a novel selective agent, nintedanib, plus standard chemotherapy in early breast cancer. METHODS: Her-2-negative breast cancer patients with tumours larger than 2 cm were eligible for dose-escalation trial (classic 3+3 method). RESULTS: The recommended phase II dose (RP2D) was 150 mg BID of nintedanib combined with standard dose of weekly paclitaxel followed by adriamycin plus cyclophosphamide. The dose-limiting toxicity was transaminase elevation. At the RP2D, the dose intensity was â¼100%. The pathologic complete response was 50%. CONCLUSIONS: The combination allows the delivery of full-dose intensity, while efficacy seems promising.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Breast Neoplasms/chemistry , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Indoles/administration & dosage , Indoles/adverse effects , Lymphopenia/chemically induced , Maximum Tolerated Dose , Middle Aged , Neoadjuvant Therapy , Neutropenia/chemically induced , Paclitaxel/administration & dosage , Prospective Studies , Receptor, ErbB-2/analysis , Treatment Outcome , gamma-Glutamyltransferase/bloodABSTRACT
Glucagonoma is an uncommon disease, a neuroendocrine tumour that develops from glucagon-producing pancreatic cells. They are usually slow-growing, but generally advanced at diagnosis, and metastatic disease is virtually incurable. Liver is the most common site of metastatic disease. We present the case of a 48-year-old man with a glucagonoma being diagnosed from a pulmonary mass. This case had no liver affection in the whole evolution of the disease, and showed a particularly aggressive course, with very little response to all therapies administered, and a survival from diagnosis of just 16 months.
Subject(s)
Glucagonoma/secondary , Lung Neoplasms/secondary , Pancreatic Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Diagnosis, Differential , Fatal Outcome , Glucagonoma/physiopathology , Glucagonoma/therapy , Humans , Lung Neoplasms/therapy , Male , Middle Aged , Pancreatic Neoplasms/physiopathology , Pancreatic Neoplasms/therapy , Tomography, X-Ray ComputedABSTRACT
Glucagonoma is an uncommon disease, a neuroendocrine tumour that develops from glucagon-producing pancreatic cells. They are usually slow-growing, but generally advanced at diagnosis, and metastatic disease is virtually incurable. Liver is the most common site of metastatic disease. We present the case of a 48-year-old man with a glucagonoma being diagnosed from a pulmonary mass. This case had no liver affection in the whole evolution of the disease, and showed a particularly aggressive course, with very little response to all therapies administered, and a survival from diagnosis of just 16 months (AU)
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Subject(s)
Humans , Male , Middle Aged , Glucagonoma/secondary , Lung Neoplasms/secondary , Pancreatic Neoplasms/pathology , Fatal Outcome , Glucagonoma/physiopathology , Glucagonoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Diagnosis, Differential , Lung Neoplasms/therapy , Pancreatic Neoplasms/physiopathology , Pancreatic Neoplasms/therapy , Tomography Scanners, X-Ray ComputedABSTRACT
Signalling pathways that emerge from EGFR activation are critical in colon cancer (CC) biology. Its targeting with specific drugs has opened a new window in the treatment of this disease. In this regard, monoclonal antibodies (mAb) have evidenced a high degree of efficiency opposed to the uselessness of tyrosine-kinase inhibitors. Cetuximab is the mAb that has evidenced most activity in CC. After its initial approval as an irinotecan-resistance reversal agent, cetuximab has demonstrated its efficiency from the first line to heavily pretreated patients. In the first line, its addition may increase response rate to chemotherapy, improving liver metastases resection rate. Another promising approach has been suggested from combination schedules with bevacizumab. Panitumumab has been recently approved for CC. Although there is limited clinical experience, the latest data have confirmed its activity in heavily pretreated patients resulting in a clinical benefit vs. best support care. In spite of the clinical benefits, adverse events and the high sanitary cost derived from these drugs force the selection of patients with the highest probability of benefit. At the moment, when EGFR expression evidenced by immunohistochemistry has no value, skin toxicity and, fundamentally, K-Ras mutations may hint at critical information for confirmatory prospective studies.
Subject(s)
Colonic Neoplasms/drug therapy , ErbB Receptors/antagonists & inhibitors , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Cetuximab , Colonic Neoplasms/etiology , Colonic Neoplasms/genetics , ErbB Receptors/analysis , ErbB Receptors/genetics , ErbB Receptors/physiology , Gene Amplification , Genes, ras , Humans , In Situ Hybridization, Fluorescence , Mutation , Panitumumab , Protein Kinase Inhibitors/therapeutic useABSTRACT
Signalling pathways that emerge from EGFR activation are critical in colon cancer (CC) biology. Its targeting with specific drugs has opened a new window in the treatment of this disease. In this regard, monoclonal antibodies (mAb) have evidenced a high degree of efficiency opposed to the uselessness of tyrosine-kinase inhibitors. Cetuximab is the mAb that has evidenced most activity in CC. After its initial approval as an irinotecan-resistance reversal agent, cetuximab has demonstrated its efficiency from the first line to heavily pretreated patients. In the first line, its addition may increase response rate to chemotherapy, improving liver metastases resection rate. Another promising approach has been suggested from combination schedules with bevacizumab. Panitumumab has been recently approved for CC. Although there is limited clinical experience, the latest data have confirmed its activity in heavily pretreated patients resulting in a clinical benefit vs. best support care. In spite of the clinical benefits, adverse events and the high sanitary cost derived from these drugs force the selection of patients with the highest probability of benefit. At the moment, when EGFR expression evidenced by immunohistochemistry has no value, skin toxicity and, fundamentally, K-Ras mutations may hint at critical information for confirmatory prospective studies (AU)
