Cytotoxic chemotherapy, particularly the regimens that contain 5‐fluorouracil (5‐FU), can produce diarrhea. Octreotide acetate appears to have a major therapeutic effect in the management of ...5‐FU‐induced diarrhea. A prospective study was conducted to investigate the efficacy of two different doses of octreotide acetate, 100 μg and 500 μg three times daily, for the treatment of severe 5‐FU‐induced diarrhea refractory to loperamide, and also to evaluate whether the higher dose is more effective in the management of this complication. Fifty‐nine patients with tissue‐documented colorectal and head and neck carcinoma were enrolled in this study, 28 in the 100 μg arm and 31 in the 500 μg arm of octreotide acetate which was administered s.c. three times daily. Patients were required to have National Cancer Institute Common Toxicity Criteria ≥ grade 3 diarrhea secondary to treatment with the 5‐FU regimen. Octreotide acetate was well tolerated by all patients. Complete resolution of diarrhea was achieved in 17 of 28 (60.71%) patients treated with 100 μg, and in 28 of 31 (90.32%) patients treated with 500 μg of octreotide (p < 0.05). This study suggests a significant benefit in the treatment of 5‐FU‐induced diarrhea in favor of the 500 μg versus the 100 μg arm. These results support the dose‐response effect of octreotide acetate. Even though higher doses of octreotide are more expensive, the cost saved in reduced hospitalization makes the higher dose more cost‐effective.
In the present phase II study we evaluated the docetaxel-ifosfamide-carboplatin (DICb) combination in the outpatient setting in patients with advanced non-small-cell lung cancer (NSCLC).
Patients ...with advanced NSCLC (stages IIIB/IV), WHO performance status (PS) <2, and no prior chemotherapy were eligible. Chemotherapy drug doses were: docetaxel: 80 mg/m2, ifosfamide: 3.5 g/m2, and carboplatin at a target area under the curve of 5 (based on Calvert's formula), all on day 1, followed by prophylactic G-CSF.
Fourty patients were entered and all are evaluable for response and toxicity: median age: 64 (48-72); PS: 1 (0-1); gender: 29 males/11 females; stages: IIIB: 13 (33%), IV: 27 (67%). Metastatic sites at diagnosis included: lymph nodes: 25; bone: 7; liver: 4; brain: 5; lung nodules: 13; adrenals: 6. Responses were as follows: 22/40 55%; 95% confidence interval (CI), 54-81% evaluable patients responded: 4 complete responses, 18 partial responses, 11 had stable disease, and 7 had progressive disease. The median response duration was 7 months (range 2-14 months), median time to progression 9 months (range 2-18 months) and median overall survival 11 months (range 3-46+ months). 1-year survival was 47.5%. Grade 3/4 toxicities included: neutropenia 28/40, with 12 developing grade 4 and 12% febrile neutropenia, thrombocytopenia grade 3: 3/40 and grade 4: 1/40, no grade 3 neuropathy, grade 1 CNS toxicity in 3, no renal toxicity, 8 grade 2 diarrhea and 4 grade 3 vomiting.
In the present phase II study the DICb combination yielded important activity and good tolerability in advanced NSCLC.
Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking.
We created a ...European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models.
Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7–87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%–95%) and mean tumor mutational burden was 7.06 (range: 0–18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767–771, 83.1%) and the far loop (codons 771–775, 13%) and only in 3.9% within the C helix (codons 761–766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osimertinib, 64.8% with poziotinib, and 76.9% with mobocertinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT ± IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03).
EXOTIC represents the largest academic real-world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit than CT plus or minus IO.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The ability to effectively define disease status in ovarian cancer after initial therapy or to selectively screen high-risk populations remains a major challenge for in vivo monoclonal antibody ...(mAb)-targeted approaches. Antitumour murine mAbs (HMFG1, HMFG2, H317, and H17E2) and the reshaped human antibody Hu2PLAP (against placental alkaline phosphatase; PLAP), labelled with indium-111 and iodine-123, were evaluated for their ability to localise ovarian tumours in sequential studies of our group. Thirty patients with ovarian cancer, aged 40-78 years (median 60 years) were studied with HMFG1/G2: 11, and H317/H17E2: 19 murine mAbs. Six patients with ovarian cancer aged between 36 and 65 years (median 49 years) were studied with the reshaped human Hu2PLAP mAb (5 patients) or the murine H17E2 mAb (2 patients) labelled with 111In via a new macrocyclic chelating agent (DOTA). One of these was imaged twice, with H17E2- and Hu2PLAP-DOTA-111In, respectively. In 20 out of 22 patients with radiologically measurable ovarian cancer, the presence of tumour was confirmed by the murine mAb scan and correlated well with the findings of conventional radiology diagnostic methods. One of these patients with a negative H17E2 scan and a large abdominal mass at laparotomy was found to have a PLAP-negative tumour on immunohistochemistry. Additionally, the antibody scan revealed the presence of active disease, confirmed at laparotomy/laparoscopy, in 6 out of 8 patients considered to be in clinical complete remission. Best images were obtained at 24 and 48 h after the 123I and 111In mAbs, respectively. Successful imaging with the reshaped human antibody, Hu2PLAP, was seen in 2 patients with PLAP-positive tumours. Antibodies to DOTA developed in 2 patients. In conclusion, immunolocalisation of ovarian tumours is feasible with both murine and reshaped human mAbs. The sensitivity and specificity of the method appear very high in this pilot study, and in view of the absence of toxicity, the diagnostic contribution of this approach should be evaluated prospectively. Given the low number of patients without surgically detectable disease in the present study, future investigations should include more patients with no evidence of disease in order to provide more meaningful estimates of specificity.
The aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC). Between 2005 and 2008, 441 patients were enrolled, with 408 ...patients being eligible. After a median follow-up of 74.7 months, 3-year DFS was 79.8 % (95 % CI 76.5-83.4) in the FOLFOX group and 79.5 % (95 % CI 75.9-83.1) in the CAPOX group (p = 0.78). Three-year OS was 87.2 % (95 % CI 84.1-91.1) in the FOLFOX and 86.9 % (95 % CI 83.4-89.9) in the CAPOX group (p = 0.84). Among 306 available tumors, 11.0 % were dMMR, 34.0 % KRAS mutant and 4.9 % BRAF mutant. Multivariate analysis showed that primary site in the left colon, earlier TNM stage and the presence of anemia at diagnosis were associated with better DFS and overall survival (OS), while grade one-two tumors were associated with better OS. Finally, a statistically significant interaction was detected between the primary site and MMR status (p = 0.010), while KRAS mutated tumors were associated with shorter DFS. However, the sample was too small for safe conclusions. No significant differences were observed in the efficacy of FOLFOX versus CAPOX as adjuvant treatment in high-risk stage II or stage III CRC patients, but definitive conclusions cannot be drawn because of the small sample size.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The expressions of p27 Kip1 (p27) and p21 Waf1 (p21) cyclin-dependent kinase inhibitors and p53 were examined in a series of 170 node-negative breast carcinomas (NNBCs)
to evaluate their prognostic ...significance. Low nuclear (p27TN) and cytoplasmic (p27TC) p27 expressions were noted in 66% and
81% of NNBCs, respectively. p21 and p53 overexpressions were detected in 56% and 26%, respectively. Low p27TN was significantly
associated with high grade (p=0.001), age â¤50 years (p=0.01), negative hormone receptors (p<0.001), low p27TC (p<0.001) and
p53 overexpression (p=0.02). Low p27TC was associated with negative hormone receptors (p<0.001). p53 overexpression was associated
with high grade (p<0.001) and negative hormone receptors (p<0.001). p21 overexpression, although not correlated with the examined
parameters, was associated with increased disease-free survival in univariate analysis. In multivariate analysis, p27TN, p27TC,
p21 and p53 were not associated with disease-free survival or overall survival. These findings argue against the prognostic
value of p27, p21 and p53 in NNBC.
Immunologic effects of high-dose interferon are still unclear. We have evaluated changes in blood lymphocyte subpopulations, immunoglobulins, and multiple interleukin in patients with high-risk ...cutaneous melanoma on adjuvant treatment with high-dose interferon and compared pretreatment values with normal controls. Samples were obtained before treatment, 1 month after induction treatment and at 3, 6, and 12 months of maintenance treatment from 24 patients with high-risk melanoma. Lymphocyte subpopulations were measured by flow cytometry and interleukin and immunoglobulin levels by radioimmunoassay. A statistically significant reduction in B-lymphocytes (p < 0.001), natural killer (NK) cells (p = 0.0004), and monocytes (p = 0.04), and an elevation in CD4/CD8 ratio (p < 0.0001) was observed after 1 month of intravenous interferon. No changes were seen in CD3, CD4, and CD8 lymphocytes. No changes in interleukin (IL)-2, -4, or -5 were observed during 1 year of treatment. IL-2 pretreatment levels were significantly lower than healthy blood donors (p = 0.001), and IL-5 pretreatment levels were significantly higher (p = 0.0056). IL-10 levels significantly dropped after 6 months of treatment (p = 0.01). Immunoglobulins (IgG, IgA, IgM) remained within normal ranges. Three patients had elevated pretreatment levels of IgE. There is a time- and dose-dependent impact of interferon on numbers of circulating B lymphocytes, NK cells, monocytes, and CD4/CD8 ratio. Defects in cellular and humoral immunity are suggested by the low IL-2 and high IL-5 levels, measured in patients with melanoma as compared with healthy controls.
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