Reliability of patient-reported toxicities during adjuvant chemotherapy.

BACKGROUND: Patient-reported outcomes (PROs) are validated tools to assess the impact of efficacy and toxicities of cancer treatments on patients' health status. Because of the demonstrated little reliability of humans in reporting memories of painful experiences, this work explores the reliability of cancer patients in reporting chemotherapy-related toxicities. AIM: This study aims to evaluate the concordance between toxicities experienced by the patients during chemotherapy and toxicities reported to the doctor at the end of the cycles. METHODS: Questionnaires concerning chemotherapy-related toxicities were administered on days 2, 5, 8, 11, 14, and 17 of each chemo cycle and at the end of the same cycle to patients undergoing adjuvant chemotherapy. The co-primary end-points were Lins's concordance correlation coefficient (CCC) and mean difference between real-time and retrospective toxicity assessments. RESULTS: In total, 7182 toxicity assessments were collected from 1096 questionnaires. Concordance was observed between the retrospective evaluations and the toxicity assessments at early (day 2), peak (maximum toxicity), late (day 14 or 17), and mean real-time evaluations for each chemotherapy cycle (CCC for mean ranging from 0.52 to 0.77). No systematic discrepancy was found between real-time and retrospective evaluations, except for peak, which was systematically underestimated retrospectively. CONCLUSIONS: Toxicities reported by the patients to the doctor at the end of each chemotherapy cycle reflect what they actually experienced without any substantial distortion. This result is very relevant both for the clinical implications in daily patients' management and in the light of the current growing impact on digital monitoring of PROs.

Phase II study of NGR-hTNF, a selective vascular targeting agent, in patients with metastatic colorectal cancer after failure of standard therapy.

BACKGROUND: NGR-hTNF consists of human tumour necrosis factor (hTNF) fused with the tumour-homing peptide Asp-Gly-Arg (NGR), which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels. Preclinical antitumour activity was observed even at low doses. We evaluated the activity and safety of low-dose NGR-hTNF in colorectal cancer (CRC) patients failing standard therapies. PATIENTS AND METHODS: Thirty-three patients with progressive disease at study entry received NGR-hTNF 0.8 µg/m(2) given intravenously every 3 weeks. The median number of prior treatment regimens was three (range, 2-5). One-quarter of patients had previously received four or more regimens and two-thirds targeted agents. Progression-free survival (PFS) was the primary study objective. RESULTS: NGR-hTNF was well tolerated. No treatment-related grade 3 to 4 toxicities were detected, most common grade 1 to 2 adverse events being short-lived, infusion-time related chills (50.0%). One partial response and 12 stable diseases were observed, yielding a disease control rate of 39.4% (95% CI, 22.9-57.8%). Median PFS and overall survival were 2.5 months (95% CI, 2.1-2.8) and 13.1 months (95% CI, 8.9-17.3), respectively; whereas in patients who achieved disease control the median PFS and overall survival were 3.8 and 15.4 months, respectively. In an additional cohort of 13 patients treated at same dose with a weekly schedule, there was no increased toxicity and 2 patients experienced PFS longer than 10 months. CONCLUSION: Based on tolerability and preliminary evidence of disease control in heavily pretreated CRC patients, NGR-hTNF deserves further evaluation in combination with standard chemotherapy.

Is one Gy equal to one Gy in chemo-radiotherapy or hormono-radiotherapy?

The biological effect induced in the cell by a fixed dose of radiotherapy (e.g. 1 Gy) can be increased, reduced or significantly altered when chemotherapeutic or hormonal agents interact. A different timing of the combination between chemo/hormonotherapy and radiotherapy may also influence the cascade of effects induced by the dose of 1 Gy. Furthermore, patient, tumor and treatment-related factors are individual parameters which should be carefully considered for their potential impact on the radiation dose.

Measures of late effects in conservative treatment of breast cancer with standard or hypofractionated radiotherapy.

AIMS AND BACKGROUND: To confirm the equivalence in terms of late effects between two fractionation schedules of radiotherapy in conservative treatment of breast cancer. METHODS: Fifty-eight patients treated at our institution from 1999 to 2002, with a median follow-up of 15 months (range, 7-46 months), were evaluated retrospectively. Twenty-nine patients (group A) were treated with standard fractionation: 5000 cGy/25fx/5 weeks, and 29 patients (group B) were treated with a hypofractionated schedule: 4500 cGy/15fx/5 weeks, three fractions per week. Late effects were evaluated using the LENT-SOMA scoring scale. The cosmetic results were assessed on a five-point scale. Skin elasticity was measured using a dedicated device (Cutometer SEM 575). RESULTS: There were no differences in breast volume, age at diagnosis and follow-up between groups. The LENT-SOMA toxicity observed in groups A and B, respectively, was as follows: grade 2-3 pain in five patients in each group; grade 2 breast edema in two and three patients; grade 2-3 and grade 2 fibrosis in six and eight patients; grade 2 and grade 2-3 telangiectasia in two and three patients; grade > or = 2 and 2 arm edema in two and one patients; no ulceration or atrophy were observed. Two patients in group A and one patient in group B needed treatment for breast and arm edema and arm edema, respectively. Very good, good-acceptable, and poor cosmetic results were observed in seven and two, fifteen and nineteen, and six and eight patients, respectively. Median skin elasticity loss due to treatment was -4.19% in group A and -6.29% in group B. These results are not statistically different. CONCLUSIONS: LENT-SOMA toxicities were minimal and no differences were observed between groups. Few patients in the hypofractionated group had very good cosmetic results, but it is debatable if radiotherapy was the only cause. Skin elasticity was not different between groups. Our results seem to suggest that it is possible to treat patients with both schedules, with similar late toxicity.