Vaccine third dose and cancer patients: necessity or luxury?

The current state of the SARS-CoV-2 pandemic is an equilibrium between expanding vaccine coverage on the one hand, and emergence of variants of concern which compromise vaccine effectiveness and enhance viral transmission on the other. Inequity in vaccine distribution, primarily an ethical issue, challenges this equilibrium, as industrialized countries prepare to administer a third booster dose to their population. Solid tumor cancer patients typically respond well to initial full vaccination and someone could argue that they should not be prioritized for an adjuvant third dose, since protection from severe disease has largely been achieved with the two-dose regimen. Nevertheless, their immune status is dynamic and not all of them exhibit an adequate immune response. A booster third dose is necessary for the inadequate responders, while it will result in better protection of all patients from mild disease as well, which if presented could have ominous consequences due to their overall frailty, and their need to adhere to strict therapeutic schemes. International scientific and public health communities should develop approaches that allow for wide immediate vaccination coverage of the developing world, in parallel with administration of adjuvant doses to solid tumor cancer patients (and other at-risk categories) of the developed nations, in order to avoid prolonging the pandemic, which will be prospectively against cancer patients' best interest.

Association of the advanced lung cancer inflammation index (ALI) with immune checkpoint inhibitor efficacy in patients with advanced non-small-cell lung cancer.

BACKGROUND: The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. RESULTS: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. CONCLUSIONS: The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

Predictive value of ATP7b, BRCA1, BRCA2, PARP1, UIMC1 (RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) genes in patients with epithelial ovarian cancer who received platinum-taxane first-line therapy.

To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR. Most of the patients (172 out of 187) received front-line carboplatin-paclitaxel regimen. Expression levels were correlated with overall (OS) and progression-free (PFS) survival by multivariate analysis. Patients with high TXN and THBS1 expression presented longer PFS (P=0.001 and P<0.001, respectively) and OS (P=0.024 and P<0.001, respectively). High TXR1 expression was associated with decreased PFS (P<0.001) and OS (P<0.001). Multivariate analysis demonstrated that high PRR13/low THBS1 expression was an independent factor for decreased PFS (hazards ratio: 1.94; 95% confidence interval (CI): 1.48-2.92; P=0.008) and OS (hazard ratio: 3.89; 95% CI: 2.16-6.87; P<0.001), whereas low TXN expression was correlated with decreased PFS (hazard ratio: 1.44; 95% CI: 1.05-2.84; P=0.043) and OS (hazard ratio: 2.38; 95% CI: 1.78-2.77; P=0.009). These findings indicate that PRR13/THBS1 and TXN expression could be used for the prediction of resistance to treatment of EOC patients and, therefore, merit to be further evaluated.

KRAS, NRAS, BRAF mutation comparison of endoscopic and surgically removed primary CRC paired samples: is endoscopy biopsy material adequate for molecular evaluation?

BACKGROUND: An everyday clinical practice dilemma in the 20-30% of metastatic colorectal cancer (CRC) patients that have not been operated on their primary tumour, is, under which specific histopathology and molecular circumstances, an endoscopic biopsy could be considered adequate to provide a representative RAS/BRAF molecular status to guide treatment. METHODS: A consecutive series of 193 paired biopsy and primary CRC tumour samples between August 2008 and 2010 available in the Department of Pathology archives, University Hospitals, KU Leuven were retrieved. For a pair to be included, in the endoscopic biopsy, 20% of invasive adenocarcinoma cells should be present and enough slides to yield an extracted DNA concentration of ⩾5 ng µl(-1), and no <2 ng µl(-1) should be available for cutting. Exons 2-4 KRAS/NRAS, BRAF, PIK3CA molecular evaluation was performed with RT-PCR and Sequenom. RESULTS: From 165 deemed adequate by the pathologist pairs, 85 (51.5%) were concordantly mutated in at least one of the tested genes, 70 (42.5%) were wt and 10 (6%) were discordant, harbouring a mutation in the primary and not in the endoscopic biopsy. In the re-evaluation, when more slides were cut per discordant pair, mutational status changed in two of the six discordantly KRAS-mutated pairs. A strong strength of agreement for both runs was observed (Cohen's kappa, k=0.877, P<0.001 and k=0.901, P<0.001, respectively) between the surgically acquired and the endoscopic biopsy specimens' evaluation. CONCLUSIONS: Based on our results, an endoscopic biopsy could provide an accurate mutational profile and become a justified alternative to a surgically removed primary tumour specimen, as long as specific histopathology criteria are met.

Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial.

BACKGROUND: Although colon cancer (CC) with microsatellite instability (MSI) has a more favorable prognosis than microsatellite stable (MSS) CC, the impact varies according to clinicopathological parameters. We studied how MSI status affects prognosis in a trial-based cohort of stage II and III CC patients treated with 5-fluorouracil (5-FU)/leucovorin or FOLFIRI. MATERIALS AND METHODS: Tissue specimens of 1254 patients were tested for 10 different loci and were classified as MSI-high (MSI-H) when three or more loci were unstable and MSS otherwise. Study end points were overall survival (OS) and relapse-free survival (RFS). RESULTS: In stage II, RFS and OS were better for patients with MSI-H than with MSS CC [hazard ratio (HR) 0.26, 95% CI 0.10-0.65, P = 0.004 and 0.16, 95% CI 0.04-0.64, P = 0.01). In stage III, RFS was slightly better for patients with MSI-H CC (HR 0.67, 95% CI 0.46-0.99, P = 0.04), but the difference was not statistically significant for OS (HR 0.70, 95% CI 0.44-1.09, P = 0.11). Outcomes for patients with MSI-H CC were not different between the two treatment arms. RFS was better for patients with MSI-H than with MSS CC in the right and left colon, whereas for OS this was significant only in the right colon. For patients with KRAS- and BRAF-mutated CC, but not for double wild-type patients, RFS and OS were significantly better when the tumors were also MSI-H. An interaction test was statistically significant for KRAS and MSI status (P = 0.005), but not for BRAF status (P = 0.14). CONCLUSIONS: Our results confirm that for patients with stage II CC but less so for those with stage III MSI-H is strongly prognostic for RFS and OS. In the presence of 5-FU treatment, stage II patients with MSI-H tumors maintain their survival advantage in comparison with MSS patients and adding irinotecan has no added benefit. CLINICALTRIALS.GOV IDENTIFIER: NCT00026273.

ERCC1 expression correlated with EGFR and clinicopathological variables in patients with non-small cell lung cancer. An immunocytochemical study on fine-needle aspiration biopsies samples.

PURPOSE: Expression of ERCC1 has not been well described in fine-needle aspiration biopsies (FNABs) in patients with non-small cell lung cancer (NSCLC). We investigated the expression of ERCC1 in correlation with EGFR expression and clinicopathological factors in patients with NSCLC in order to determine if these play a role in the prognosis of the disease. METHODS: We studied 45 patients, 34 with adenocarcinoma and 11 with squamous cell carcinoma. Of these 45 patients, 35 were males and 10 females, aged between 45 and 83 years, 30 smokers and 15 non-smokers. Eighteen (18) tumors were of stage I, twelve (12) stage II and fifteen (15) stage III. To investigate the expression of ERCC1 and EGFR (scores 0, 1, 2, 3), immunocytochemistry was performed on air dried specimens (FNABs) using monoclonal antibodies by alkaline-phosphatase (APAAP) method. RESULTS: ERCC1 expression was detected in tumors from 27 patients (60%) and EGFR in 10 patients (22.2%). ERCC1 was expressed more frequently in males (65.7%) in patients >65 years old (64%), in smokers (66.7%) and in stage I (66.7%). Negative ERCC1 expression was significantly associated with the presence of EGFR. EGFR was expressed only in adenocarcinomas and more frequently in women (70%) and non smokers (53.3%). CONCLUSIONS: ERCC1 expression was identified as positive (scores 2+ and 3+) in the majority of NSCLCs and seems to be an independent prognostic marker of longer survival. In addition EGFR expression was positive (scores 2+ and 3+) in the minority of NSCLCs and only in adenocarcinomas, more frequently in ERCC1-negative (scores 0 and 1+) tumors, suggesting that it is not an independent prognostic marker for the outcome of the patients suffering from NSCLC.

The eminent dermatologist Moriz Kaposi (1837-1902) and the first description of idiopathic multiple pigmented sarcoma of the skin.

In 1872, the Hungarian born dermatologist Moriz Kaposi that was practicing in Vienna first described a rare endemic disease that bears his name, among elderly persons of Central European or Mediterranean origin named "idiopathic multiple pigmented sarcoma of the skin". Ten years later the Italian dermatologist Tommaso de Amicis confirms Kaposi's findings. For more than a century the disease was known as a rare low grade malignancy till the 1980s AIDS epidemic.

The great surgeon Jean-Louis Faure (1863-1944) and his contribution in the treatment of uterine cancer.

At the beginning of the 20th century, Professor Jean-Louis Faure, one of the leading surgeons of the innovative Parisian Medical School, published an exhaustive work on uterine cancer. He was the first to perform in France the procedure of total abdominal hysterectomy by median section of the uterus contributing to the evolution of cancer surgery.

A triplet combination with irinotecan (CPT-11), oxaliplatin (LOHP), continuous infusion 5-fluorouracil and leucovorin (FOLFOXIRI) plus cetuximab as first-line treatment in KRAS wt, metastatic colorectal cancer: a pilot phase II trial.

BACKGROUND: We conducted an open-label, pilot phase II trial to evaluate the efficacy and safety of FOLFOXIRI plus cetuximab as first-line treatment of patients with metastatic colorectal cancer (mCRC). METHODS: Thirty patients with KRAS wild-type mCRC, <70 years and with performance status 0-1 were included in the trial. RESULTS: Complete and partial responses were observed in 4 (13.3%) and 17 (56.7%) patients, respectively (overall response rate (ORR)=70%; 95% confidence interval (CI): 53.6%-86.4%); 8 patients (26.7%) had stable disease and 1 had progressive disease. The median time to tumour progression was 10.2 months (95% CI: 7.1-13.4) and the overall median survival time was 30.3 months (95% CI: 18.8-41.9). Secondary R0 resection was performed in 11 (37%) patients. Grade 3 or 4 diarrhoea and neutropenia were observed in 16 (53%) and 7 (23.3%) patients, respectively, and febrile neutropenia observed in 2 (6.6%) patients. Neurotoxicity grade 2 or 3 was reported in 7 (23.3%) and in 2 (6.7%) patients, respectively, and grade 3 rush was reported in 1 patient. CONCLUSION: The FOLFOXIRI/cetuximab combination presented increased activity in terms of response rate and R0 secondary liver metastases resection, and merits further investigation, especially in patients with initially unresectable disease confined to the liver.

Cytopathologic interpretation of ascites due to malignancy.

The diagnosis of metastatic cancer in peritoneal fluid is of great importance for the patient and the attending physician. A cytopathologist's responsibility is twofold: (1) to accurately identify malignant cells; (2) to interpret tumor type and if possible the site of its origin even in the absence of complete clinical history of other clues. The difficulty in the diagnosis of metastatic neoplasms in peritoneal fluid is due to 2 factors: (1) abnormal mesothelial cells or macrophages may simulate cancer cells, or may conceal tumor cells; and (2) peritoneal fluid constitutes a natural and hitherto inadequately explored medium of cell culture, in which neoplastic cells may proliferate free of the boundaries imposed upon them by the framework of organs and tissues. Immunocytochemistry (ICC) and molecular techniques are essential to establish an accurate diagnosis. From a great many points of view malignant peritoneal fluid is suitable for continuous study of cancer cells, thus providing knowledge about biologic aspects of human solid tumors.

Metronomic vinorelbine plus bevacizumab as salvage therapy for patients with metastatic breast cancer.

PURPOSE: Continuous administration of oral vinorelbine, given 3 times a week (metronomic), is feasible and exceptionally well tolerated at doses up to 50 mg with clinical activity against refractory tumors. In this phase II study oral metronomic vinorelbine and bevacizumab were evaluated as salvage therapy in women with pretreated metastatic breast cancer (MBC). METHODS: Patients received oral vinorelbine (50 mg 3 times a week) and bevacizumab (10 mg/kg) biweekly in cycles of 28 days. The primary endpoint was objective response rate (ORR). A preplanned analysis was performed when the first 13 patients were evaluated for tumor response. RESULTS: One patient (7.7%) achieved partial response (PR) and 6 (46.1%) stable disease (SD). The combination was very well tolerated but, as per protocol, the study was closed prematurely due to lack of efficacy. CONCLUSION: The combination of oral metronomic vinorelbine and bevacizumab has good tolerance but minimal activity in terms of objective responses in pretreated patients with MBC.

BRAF mutations, microsatellite instability status and cyclin D1 expression predict metastatic colorectal patients' outcome.

BACKGROUND: The significance of BRAF mutations, microsatelite instability (MSI) status and cyclin D1 expression in patients with metastatic colorectal cancer (mCRC) was evaluated. METHODS: Primary tumours from 144 patients treated for mCRC were assessed for BRAF (V600E) mutation, MSI status and cyclin D1. The data were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: BRAF mutations were detected in 10 (out of 22, 45%) patients with MSI-H tumours compared with 2 (out of 122, 1.6%) in those with microsatellite stable tumours (P<0.001). The presence of BRAF mutations was correlated with cyclin D1 overexpression (7 out of 26 patients, 58% vs 5 out of 118 patients, 14%; P=0.001). Patients with BRAF-mutated primary tumours had a significantly decreased PFS (2.7 vs 9.8 months; P<0.001) and median OS (14 vs 30 months; P<0.001) than patients with wild-type (wt) tumours. Patients with MSI-H and BRAF-mutated tumours experienced significantly lower PFS (3.1 vs 11.4 months; P=0.008) and OS (14.5 vs 35.5 months; P=0.004) than patients with MSI-H and BRAF wt tumours. Similarly, BRAF mutations and cyclin D1 overexpression were correlated with decreased PFS (3.1 vs 8.6 months; P=0.03) and OS (17.8 vs 39.2 months; P=0.01). CONCLUSION: BRAF V600E mutations are associated with MSI-H status and cyclin D1 overexpression and characterize a subgroup of patients with poor prognosis.

Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer.

BACKGROUND: We address the prognostic and predictive value of KRAS, PIK3CA and BRAF mutations for clinical outcomes in response to active agents in the treatment of metastatic colorectal cancer (mCRC). METHODS: We determined KRAS, BRAF and PIK3CA mutations in tumours from 168 patients treated for mCRC at two institutions. All patients received 5-FU-based first-line chemotherapy and treatment outcome was analysed retrospectively. RESULTS: KRAS, BRAF and PIK3CA mutations were present in 62 (37%), 13 (8%) and 26 (15%) cases, respectively. Multivariate analysis uncovered BRAF mutation as an independent prognostic factor for decreased survival (hazard ratio (HR) 4.0, 95% confidence interval (CI) 2.1-7.6). In addition, patients with BRAF-mutant tumours had significantly lower progression-free survival (PFS: HR 4.0, 95% CI 2.2-7.4) than those whose tumors that carried wild-type BRAF. Among 92 patients treated using chemotherapy and cetuximab as salvage therapy, KRAS mutation was associated with lack of response (P=0.002) and shorter PFS (P=0.09). BRAF (P=0.0005) and PIK3CA (P=0.01) mutations also predicted reduced PFS in response to cetuximab salvage therapy. CONCLUSIONS: These results underscore the potential of mutational profiling to identify CRCs with different natural histories or treatment responses. The adverse significance of BRAF mutation should inform patient selection and stratification in clinical trials.

Dose escalating clinical study of high dose infusional 5-fluorouracil and leukovorin (AIO regimen) plus alternate weekly administration of oxaliplatin and irinotecan in patients with advanced tumors of the gastrointestinal tract.

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) of weekly high dose 5-fluorouracil (5FU) continuous infusion and leukovorin (LV) alternatively combined with oxaliplatin and irinotecan in patients with advanced tumors of the gastrointestinal (GI) tract. PATIENTS AND METHODS: Patients received a fixed dose of LV (500 mg/m(2)) over 2 h infusion on weeks 1 to 4 and escalated doses of: oxaliplatin (starting dose 65 mg/m(2): 120 min i.v. infusion on weeks 1 and 3); irinotecan (starting dose 80 mg/m(2); 90 min i.v. infusion on weeks 2 and 4) and 5FU (starting dose 1500 mg/m(2); 22 h continuous i.v. infusion, on weeks 1 to 4), in cycles of 5 weeks. DLTs were evaluated during the fi rst cycle. RESULTS: Twenty-eight patients were treated on 8 dose levels and all but two patients received the regimen at least as second-line treatment. The DLT level was reached at the oxaliplatin dose of 90 mg/m(2), irinotecan dose of 110 mg/m(2), LV dose of 500 mg/m(2) and 5FU dose of 1750 mg/m(2); the recommended MTDs were 85 mg/m(2) for oxaliplatin, 110 mg/m(2) for irinotecan, 1750 mg/m(2) for 5FU and 500 mg/m(2) for LV. Grade 3 or 4 diarrhea and grade 3 nausea/vomiting were the dose-limiting events. Diarrhea was the most common toxicity of the regimen, occurring in 12 (42.8%) patients. Hematological toxicity was mild and there were no treatment- related deaths. CONCLUSION: This weekly regimen showed a favorable toxicity profile and merits further investigation in patients with advanced/metastatic tumors of the GI tract.

A dose escalation study of gemcitabine plus pemetrexed administered biweekly in patients with solid tumors.

PURPOSE: The study aimed to determine the maximum tolerated doses (MTDs) and identify the dose-limiting toxicities of the biweekly administration of pemetrexed plus gemcitabine in patients with solid tumors. PATIENTS AND METHODS: Patients with advanced malignancies were treated with escalated doses of gemcitabine and pemetrexed (starting doses 1,250 and 300 mg/m(2), respectively) both given on days 1 and 15 in cycles of 4 weeks. RESULTS: Forty-one patients were treated at 7 dose levels. The MTD was reached at the dose of 1,750 mg/m(2) for gemcitabine and 450 mg/m(2) for pemetrexed. Dose-limiting events were grade IV neutropenia, febrile neutropenia and treatment delay due to grade III hematological toxicities. One partial response in a pretreated patient with ovarian cancer was observed, while 4 other patients experienced stable disease. CONCLUSIONS: The biweekly administration of gemcitabine plus pemetrexed at the recommended MTDs is safe, well tolerated and demonstrates antitumor activity which merits further evaluation in phase II studies.

Endothelial p21(WAF1/CiP1) cell cycle inhibitor is down-regulated in breast cancer.

BACKGROUND: Tumor angiogenesis is considered a multi-pathway process, while p21(WAF1/CiP1) is a CDK inhibitor involved in cell division and survivaL Herein the tumor environment effect on endothelial p21(WAF1/Cip1) expression is examined. MATERIALS AND METHODS: The EA.hy 926 endothelial cell line and tumor-conditioned medium (TCM) from the MDA-MB-468 breast cancer cell line were used. Endothelial cells grown alone and in TCM were immunostained for p21(WAF1/Cip1) and analyzed by RT-PCR Forty-four cases of breast cancer and forty-three cases of normal breast tissue were immunostained for p21(WAF1/Cip1). RESULTS: Endothelial p21(WAF1/Cip1) is transcriptionally down-regulated under the influence of TCM. Moreover, it seems that breast cancer tumor endothelium does not express p21(WAF1/Cip1). CONCLUSION: P21(WAF1/Cip1) plays a major role in angiogenesis, since tumor cells seem to down-regulate endothelial p21(WAF1/Cip1), compared to endothelial cells grown in serum-free medium. The verification of the tissue culture experiment results by immunohistochemistry on tissue sections indicates p21(WAF1/Cip1) as a target of modern molecular therapy.

Phase I study of weekly docetaxel and liposomal doxorubicin in patients with advanced solid tumors.

PURPOSE: To determine the maximum-tolerated doses (MTDs) and the dose-limiting toxicities (DLTs) of the weekly administration of docetaxel and pegylated liposomal doxorubicin (PEG-LD) in patients with advanced solid tumors. PATIENTS AND METHODS: Forty-eight patients with solid tumors were enrolled in the study. Dose escalations of both drugs were given on a weekly basis for 3 consecutive weeks in cycles of 4 weeks. The starting dose for docetaxel was 20 mg/m(2)/week and for PEG-LD 6 mg/m(2)/week. RESULTS: The MTD was 35 mg/m(2)/week for docetaxel and 14 mg/m(2)/week for PEG-LD. The DLTs at this level were grade 3 diarrhea (n=1 patient) and grade 3 mucositis (n=2 patients). There was no grade 4 hematologic or non-hematologic toxicity. Grade 3 neutropenia and thrombocytopenia occurred only in 1 and 2 patients, respectively. The non-hematologic toxicity was also mild with grade 2/3 fatigue in 8 patients, grade 2/3 neurotoxicity in 4, grade 2/3 mucositis in 8, grade 2/3 diarrhea in 4 and grade 2/3 nausea and vomiting in 5 patients. Two (5.7%) complete and 6 (17%) partial responses (overall response rate=22.7%; 95% confidence interval 9.6--32.4%) were observed among 35 evaluable patients. In 12 (63%) of 19 patients with hormone-refractory prostate cancer, a decline in serum levels of prostate-specific antigen of >50% was observed. CONCLUSIONS: The weekly administration of docetaxel with PEG-LD is a well-tolerated regimen that merits further evaluation.

First-line intra-arterial chemotherapy (IAC) with epirubicin and mitoxantrone in locally advanced breast cancer.

BACKGROUND: Approximately 20% of patients with breast cancer present with locally advanced disease without distant metastases. This phase II double-center trial aimed at investigating the activity of epirubicin (Farmorubicin)--mitoxantrone (Onkotrone/Novantrone) combination as first-line intra-arterial chemotherapy (IAC) in locally advanced breast cancer patients. PATIENTS AND METHODS: Thirty-six patients with locally advanced disease and no prior exposure to anthracyclines received the following regimen: epirubicin (Farmorubicin) 30 mg/mq and mitoxantrone (Onkotrone/Novantrone) 10 mg/mq by IAC short infusion on day 1, every 3 weeks for up to six cycles. Prior to IAC an arteriogram of subclavian, internal mammary and lateral thoracic arteries was obtained in all patients, followed by infusion of a blue dye solution into the arteries to determine the most appropriate vessel that supplies the tumor area. RESULTS: Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 25 patients (70%; 95%CI, 62% to 80%): 3 CR, 22 PR. Although three of the patients showed complete tumor regression, operative removal or toilet mastectomy became feasible in 25 patients since tumor shrinkage ranged over 75%. A total of 25 mastectomies were carried out for 36 patients. Four patients had bulky tumors (> 13 cm tumor diameter), while 8 patients had ulcerated tumors, two of which presented with complete infiltration of normal breast tissue. The median time to progression and median overall survival were 11 and 27 months, respectively. The time to local response was 3 weeks and time to mastectomy was 9 weeks. Transient neurological disorders developed in six patients and skin chemical burns with painful inflammatory reactions were encountered in ten patients. No systemic toxicity was observed in terms of bone marrow depression and hair loss. No cardiotoxicity was observed. In all specimens necrosis was reported (complete 3 cases, partial 16 and minimal 6). CONCLUSION: A combination of epirubicin (Farmorubicin) and mitoxantrone (Onkotrone/Novantrone) as IAC appears to be a safe and well tolerated treatment for locally advanced breast cancer without clinical evidence of distant metastases. When combined with surgery it offers interesting results in terms of local control and allows a high rate of mastectomies in otherwise inoperable cases.

Successful treatment of rhinocerebral mucormycosis with liposomal amphotericin B and surgery in two diabetic patients with renal dysfunction.

The zygomycetes are a class of fungi that can cause a variety of infections in humans. Rhinocerebral mucormycosis is a rare disease and usually affects diabetic or immunosuppressed patients. The disease progresses rapidly and is usually fatal despite aggressive surgical and medical therapy. We report the management of two cases of rhino-sinusal and orbital mucormycosis in diabetic patients on treatment with corticosteroids, and mild renal impairment, successfully treated with a combination of aggressive surgical debridement and liposomal amphotericin B.