A single institution prospective trial was conducted to evaluate the efficacy of biotherapy or chemotherapy in metastatic
neuroendocrine carcinomas (NECs). The choice of therapy was based on the ...revised histological classification criteria of the
WHO in an effort to define a standardized protocol for therapy of these cancers. Patients with well-differentiated NECs (WD-NECs;
n=11) received therapy with octreotide long-acting release and interferon-α-2b for a maximum of 1 year; cases with poorly-differentiated
NECs (PD-NECs; n=8) were given combination cisplatin, L-leucovorin and 5-fluorouracil chemotherapy for a maximum of 9 cycles.
Five patients (4 with WD-NECs) had carcinoid syndrome. Among the patients with WD-NECs (median follow-up 20 months, range
4-40), 4 had partial responses and 7 had stable disease. In patients with PD-NECs (median follow-up 10.5 months, range 3-30),
3 had partial response, 2 stable disease, and the disease progressed in 3 cases. The 2-year survival rate in WD-NECs and PD-NECs
was 88% and 66%, respectively. Grade 3-4 side-effects were limited to 9% thrombocytopenia and 12.5% neutropenia. Both these
treatment regimens had a good therapeutic index and compared favourably with those previously reported for metastatic WD-NECs
and PD-NECs.
Background
Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven ...by selection according to individual tumor molecular characteristics are expected to provide added value.
Objective
We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).
Patients and Methods
From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were
MGMT
promoter hypermethylation (48.7%),
HER2
amplification (28.8%),
BRAF
V600E
mutation (20%), and novel gene fusions involving
ALK
or
NTRK
(2.5%).
Results
One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33.
KRAS
exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known
KRAS
status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 95% CI 2.80–5.03 vs. 2.13 months 95% CI 1.77–2.87, respectively,
p
= 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with
KRAS
wild-type tumors had longer OS than those with mutated tumors (7.83 95% CI 7.33–10.80 vs. 7.18 months 95% CI 5.63–9.33, respectively,
p
= 0.06).
Conclusions
This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.
Abstract Background aims Adoptive T-cell therapy with tumor-specific T cells has emerged as a potentially useful approach for treating patients with advanced malignancies. We have demonstrated ...previously the feasibility of obtaining large numbers of autologous anti-tumor-specific cytotoxic T lymphocytes (CTL) generated by stimulation of patients' peripheral blood mononuclear cells with dendritic cells pulsed with apoptotic tumor cells Methods Six patients with progressing metastatic solid tumors (one renal cell carcinoma, two ovarian cancers, two extraosseous peripheral neuroectodermal tumors, one soft tissue sarcoma) not eligible for conventional therapies were treated with adoptive immunotherapy. Anti-tumor CTL, proven to be reactive in vitro against patient tumor cells, but not against normal cells, were infused following lymphodepleting chemotherapy administered to favor T-cell proliferation in vivo. Results Patients received a median of nine CTL infusions (range 2–19). The median number of CTL administered per infusion was 11 × 108 (range 1–55 × 108 ). No patient experienced acute or late adverse events related to CTL infusion, even when large numbers of cells were given. Post-infusion laboratory investigations demonstrated an increase in the frequency of circulating anti-tumor T-cells and, in patients with a longer follow-up receiving two CTL infusions/year, a stabilization of these values. Conclusions Our study demonstrates that autologous ex vivo -generated anti-tumor CTL can be administered safely in patients with advanced solid tumors and can improve the immunologic reactivity of recipients against tumor. These preliminary results provide a rationale for evaluating the clinical efficacy of this immunotherapeutic approach in phase I/II studies.
Unresponsiveness to erythropoiesis-stimulating agents is a major limitation to the treatment of chemotherapy-related anemia. This is often related to a disregulation of iron metabolism leading to ...functional iron deficiency. However, the use of iron supplementation during treatment with erythropoiesis-stimulating agents has not been as rigorously pursued in anemic patients with cancer as it has in chronic kidney disease. In this article, we review and discuss the role of iron supplementation in the setting of chemotherapy-related anemia in view of recently published clinical trials addressing this issue.
Myeloid colony-stimulating factors (granulocyte colony-stimulating factor G-CSF and granulocyte-macrophage colony-stimulating factor) are commonly used in clinical practice for the prevention of ...anticancer chemotherapy-induced neutropenia and its potentially life-threatening complications. Pegfilgrastim is a novel recombinant human G-CSF pharmaceutically developed by covalent binding of a polyethylene glycol molecule to the N-terminal sequence of filgrastim. Due to its unique neutrophil-mediated clearance, pegfilgrastim can be administered once per chemotherapy cycle. Clinical trials have demonstrated that a single, fixed, subcutaneous dose of pegfilgrastim is comparable in safety and efficacy to daily injections of filgrastim for decreasing the incidence of infection following myelosuppressive chemotherapy in patients with cancer. Recent trials have been conducted to evaluate the use of pegfilgrastim in different clinical settings, including support of dose-dense regimens, mobilization and transplantation of hematopoietic stem cells.
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