[Show abstract][Hide abstract] ABSTRACT: Our group evaluated the risk of recurrence for optimally treated advanced epithelial ovarian cancer (adEOC) in patients with a low-level rising serum CA-125 concentration within the normal range (0-35 kU/l). In addition, we tested the new proposed early CA-125 signal of progressive disease (EPD) criterion in the same study population.
Patients treated from 1998 to 2006 for adEOC were identified at our institution. Inclusion criteria were as follows: CA-125 at time of diagnosis (>35 kU/l); International Federation of Gynecology and Obstetrics stages III-IV treated with optimal primary treatment; and complete response (CR) to primary treatment with normalization of CA-125.
Median progression-free survival and overall survival for the recurrence group (n = 60) were 17.7 and 38.2 months, respectively. The median follow-up time from CR to last contact was 40.2 months for patients in the nonrecurrence group (n = 36). An absolute increase in serum CA-125 levels of >or=5 kU/l compared with baseline CA-125 nadir values was significantly predictive of recurrence (odds ratio for recurrence = 402.98, P < 0.0001). The progression date was predated by the EPD criterion in 77% of patients with known progressive disease (median, 58 days early) with a sensitivity of 90%, a positive predictive value of 96.4%, and a false-positive rate of 5.6%.
Among patients with optimally treated adEOC in complete remission, a low-level increase in serum CA-125 concentration within the normal range is a strong independent predictive factor for disease recurrence. In this patient population, future prospective randomized trials should consider the evaluation of the EPD criterion.
[Show abstract][Hide abstract] ABSTRACT: The prognosis of metastatic colorectal cancer (mCRC) remains poor despite the advances made in recent years with new therapeutic agents, surgical procedures, and diagnostic methods. New treatments directed toward molecular targets have emerged and are being developed to improve these results, but there is a need to optimize and define the best use of these new approaches. Cetuximab is a chimeric monoclonal antibody that binds to the epidermal growth factor receptor and thereby inhibits cell proliferation, metastasis, and angiogenesis. Preclinical studies indicate that cetuximab induces synergistic antitumor activity when combined with chemotherapy or radiation. In pretreated patients with mCRC, cetuximab might restore sensitivity toward irinotecan and has therefore been registered for the treatment of patients with mCRC refractory to irinotecan. Moreover, cetuximab seems to add substantial benefit to standard oxaliplatin- and irinotecan-based combinations, resulting in high response rates in the first-line setting. Recent preclinical and clinical data have optimized cetuximab therapy. New targeted therapy combinations and the identification of biomarkers associated with disease control in patients treated with cetuximab are changing the current management of mCRC. Also, preliminary data suggest that cetuximab can be administered in a more convenient 2-week schedule in combination with standard chemotherapy.
No preview · Article · Oct 2008 · Clinical Colorectal Cancer
[Show abstract][Hide abstract] ABSTRACT: Oxaliplatin is the only third-generation platinum derivative compound that has found a place in the routine treatment of colorectal cancer (CRC). The appearance of oxaliplatin, as well as irinotecan, in the CRC treatment armamentarium has offered new standards for adjuvant treatment and greater hopes in metastatic disease. Moreover, the combination of oxaliplatin-based chemotherapy with new targeted drugs has improved response rates and survival of these patients. Despite these new approaches, the prognosis of CRC remains poor and a better understanding of the molecular pathways is needed to optimize the use of these new approaches. In this review, the authors examine the development of oxaliplatin as well as the main trials that have positioned oxaliplatin as a key drug in the treatment of CRC.
No preview · Article · Sep 2008 · Expert Review of Anti-infective Therapy
[Show abstract][Hide abstract] ABSTRACT: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients refractory to platinum-based chemotherapy.
Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment.
Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease >/=12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit.
In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.
Preview · Article · Jun 2008 · Clinical Cancer Research
[Show abstract][Hide abstract] ABSTRACT: Case report.
We present a case of an ambulatory patient with a solitary fibrous tumor of the spinal cord.
Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor of the pleural cavity, increasingly recognized at numerous extrathoracic sites, including, among others, prostate, kidney, and thyroid. The spinal cord is an extremely rare localization of SFTs with only 17 cases reported in the literature since 1996. Although SFTs are usually indolent neoplasms that are cured with complete surgical resection, malignant transformation has been described within histologically benign SFTs. However, no cases of malignant dissemination have been described in this localization.
Discussion of the patient's clinical and radiologic history with a review of the relevant background literature.
We report the first case of spinal cord SFT with visceral dissemination years after the primary diagnosis, despite benign histologic features of the primary tumor.
This finding may indicate that long-term follow-up might be necessary in these patients. In addition, metastatic radical surgery of SFTs should be considered to achieve long-term survival since there are no currently available effective systemic therapies.
[Show abstract][Hide abstract] ABSTRACT: Salivary ductal carcinoma (SDC) is an uncommon malignant tumor of the salivary glands. Although there is no known standard of care for the treatment of advanced disease, the vast majority of patients with SDC may be offered palliative systemic therapy. We report a case of epidermal growth factor receptor 2 (HER2)-positive metastatic submandibular SDC with a complete and durable clinical response to treatment with trastuzumab in combination with chemotherapy.
A 62-year-old man was diagnosed with SDC of the left submandibular gland with extensive cervical lymph node involvement. The lesion was completely resected, and the patient underwent postoperative radiotherapy. After 6 months, multiple pulmonary metastatic lesions were detected. A complete response was reached with trastuzumab-based combination therapy, and no evidence of disease progression has been observed after 14 months of initiation of systemic therapy.
Trastuzumab-based combination therapies should be considered for advanced SDC.
[Show abstract][Hide abstract] ABSTRACT: Background: The amount of residual disease after surgery is considered the most important factor influencing the survival of patients with advanced epithelial ovarian cancer (adEOC). In optimally treated patients with adEOC, there are no well-established prognostic factors (excluding International Federation of Gynecology and Obstetrics (FIGO) stage). The aim of this retrospective study is to analyze the prognostic value of the CA-125 nadir after the completion of an optimal primary treatment. Patients and methods: Patients treated for adEOC were identified from January 1998 to December 2006. Inclusion criteria: elevated CA-125 at time of diagnosis (>35 kU/l); FIGO stage III-IV treated with optimal primary treatment (residual tumor
Full-text · Article · Jan 2008 · Annals of Oncology