Clinical efficacy of sequential treatments in KRASG12C-mutant metastatic colorectal cancer: findings from a real-life multicenter Italian study (CRC-KR GOIM).

BACKGROUND: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. PATIENTS AND METHODS: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. RESULTS: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). CONCLUSION: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.

Real-world experience of abiraterone acetate plus prednisone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: long-term results of the prospective ABItude study.

BACKGROUND: Limited real-world data exist on the effectiveness and safety of abiraterone acetate plus prednisone (abiraterone hereafter) in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) naive to chemotherapy. Most of the few available studies had a retrospective design and included a small number of patients. In the interim analysis of the ABItude study, abiraterone showed good clinical effectiveness and safety profile in the chemotherapy-naive setting over a median follow-up of 18 months. PATIENTS AND METHODS: We evaluated clinical and patient-reported outcomes (PROs) of chemotherapy-naive mCRPC patients treated with abiraterone as for clinical practice in the Italian, observational, prospective, multicentric ABItude study. mCRPC patients were enrolled at abiraterone start (February 2016-June 2017) and followed up for 3 years; clinical endpoints and PROs, including quality of life (QoL) and pain, were prospectively collected. Kaplan-Meier curves were estimated. RESULTS: Of the 481 patients enrolled, 454 were assessable for final study analyses. At abiraterone start, the median age was 77 years, with 58.6% elderly patients and 69% having at least one comorbidity (57.5% cardiovascular diseases). Visceral metastases were present in 8.4% of patients. Over a median follow-up of 24.8 months, median progression-free survival (any progression reported by the investigators), time to abiraterone discontinuation, and overall survival were, respectively, 17.3 months [95% confidence interval (CI) 14.1-19.4 months], 16.0 months (95% CI 13.1-18.2 months), and 37.3 months (95% CI 36.5 months-not estimable); 64.2% of patients achieved ≥50% reduction in prostate-specific antigen. QoL assessed by Functional Assessment of Cancer Therapy-Prostate, the European Quality of Life 5 Dimensions 3 Level, and European Quality of Life Visual Analog Scale remained stable during treatment. Median time to pain progression according to Brief Pain Inventory data was 31.1 months (95% CI 24.8 months-not estimable). Sixty-two patients (13.1%) had at least one adverse drug reaction (ADR) and 8 (1.7%) one serious ADR. CONCLUSION: With longer follow-up, abiraterone therapy remains safe, well tolerated, and active in a large unselected population.

Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study.

BACKGROUND: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. PATIENTS AND METHODS: In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. RESULTS: In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. CONCLUSION: FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.

RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial.

Background: Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. Patients and methods: In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. Results: A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis. Conclusion: This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.

Non-pegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide or vinorelbine in metastatic breast cancer not previously treated with chemotherapy:a multicenter phase III study.

We conducted a phase III multicenter randomized trial to compare the efficacy of the combination of liposome encapsulated doxorubicin (Myocet(©)) plus either cyclophosphamide (MC) or vinorelbine (MV). Since July 2006, 233 patients affected with metastatic breast cancer were randomized to receive the combination of Myocet (M) 60 mg/m(2) i.v. plus cyclophosphamide (C) 600 mg/m2 on Day 1 of a 21­day cycle (Arm A) or Myocet (M) at 50 mg/m2 plus vinorelbine (V) 25 mg/m2 i.v. on Day 1 and V 60 mg/m2 orally on Day 8 on a 21­day cycle (Arm B). The primary endpoints of the study was time to progression (TTP); secondary endpoints were RR, toxicity and OS. Response was observed in 53/116 (45.7%) evaluable patients of Arm A vs. 51/112 (45.5%) of Arm B, respectively (P=NS). Median TTP was 41 weeks (95% CI, 32­51) and 34 weeks (95% CI, 26­39), for M/C and M/V, respectively (P=0.0234). The difference in median OS was not statistically significant (131 vs. 122 weeks; P=0.107). With regard to toxicity, patients treated with MV showed a slight increase of neutropenia and constipation, as compared to those treated with MC. No clinical signs of cardiotoxicity were observed. The MC combination remains as an unbeaten 'standard' in first line treatment of MBC.

Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation status by next-generation sequencing: findings from the CAPRI-GOIM trial.

BACKGROUND: Treatment with antiepidermal growth factor receptor (anti-EGFR) monoclonal antibodies has been restricted to metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors. Next-generation sequencing (NGS) allows the assessment in a single analysis of a large number of gene alterations and might provide important predictive and prognostic information. PATIENTS AND METHODS: In the CAPRI-GOIM trial, 340 KRAS exon 2 wild-type mCRC patients received first-line FOLFIRI plus cetuximab. Tumor samples (182/340, 53.5%) were assessed by NGS to search for mutations in 22 genes involved in colon cancer. RESULTS: Objective responses in the NGS cohort were observed in 104/182 patients [overall response rate (ORR) 57.1%; 95% confidence interval (95% CI) 52% to 66.4%] with a median progression-free survival (mPFS) of 9.8 (95% CI 8.7-11.5) months. NGS analysis was successfully completed in all 182 samples. One or more gene mutations (up to five) were detected in 124/182 (68.1%) tumors within 14/22 genes for a total of 206 mutations. KRAS exon 2 mutations were identified in 29/182 (15.9%) samples, defined as wild type by local laboratory assessment. Frequently mutated genes were: TP53 (39.6%), KRAS exons 3/4 (8.8%), NRAS exons 2/3 (7.1%), PIK3CA exons 9/20 (13.2%), BRAF (8.2%). FOLFIRI plus cetuximab treatment determined ORR of 62.0% (95% CI 55.5% to 74.6%) with mPFS of 11.1 (95% CI 9.2-12.8) months in patients with KRAS and NRAS wild-type tumors. Conversely, ORR was 46.6% (95% CI 39.9-57.5%) with mPFS of 8.9 (95% CI 7.4-9.6) months in patients with KRAS or NRAS mutations. Similarly, the subgroup of patients carrying KRAS, NRAS, BRAF, or PIK3CA mutations showed a worse outcome, although this might be due to a prognostic effect. CONCLUSIONS: This study demonstrates that NGS analysis in mCRC is feasible, reveals high level of intra and intertumor heterogeneity, and identifies patients that might benefit of FOLFIRI plus cetuximab treatment.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: long term results of the Italian Tamoxifen Anastrozole trial.

The Italian Tamoxifen Anastrozole (ITA) trial investigated the efficacy of switching to anastrozole for women who were already on adjuvant tamoxifen since 2-3years. Relapse-free survival (RFS) was the primary end-point; event-free survival (EFS), overall survival (OS) and safety were secondary end-points. Herein, we report an update on the long term results of this trial. At a median follow-up time of 128 months (range 14-168 months), 94 events have been recorded in the tamoxifen group compared with 71 events in the anastrozole group (hazard ratio (HR)=0.71; 95% confidence interval (CI), 0.52-0.97; p=0.03). RFS was also significantly longer in the anastrozole group (HR=0.64; 95% CI, 0.44-0.94; p=0.023); no statistically significant difference between study arms concerning OS was shown, but the trial was not powered enough in respect to this end-point. The incidence of serious adverse events (SAE) like bone fractures was comparable (four in each arm), while gynaecological problems were still significantly more numerous among the women continued on tamoxifen (21 patients developed a SAE in this group, including eight endometrial cancers, compared to three patients who suffered from a SAE, including one endometrial cancer, in the anastrozole group: p<0.000). Present data confirm that switch is safe and can provide long-term gain in terms both of RFS and of EFS, which persists even several years since treatment discontinuation.

A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or metastatic breast cancer.

AIM: To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6-8 cycles of Myocet® 50 mg/m2 (day 1), docetaxel 30 mg/m2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were assessed according to World Health Organisation criteria. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure and/or a decrease in left ventricular ejection fraction (LVEF). RESULTS: The overall response rate was 55.6% (complete response 8.9%, partial response 46.7%), with a median time-to-progression of 10.9 months (C.I. 8.7-15.0). Median overall survival was not reached. The most frequent grade 3-4 adverse events were granulocytopaenia (60.0%), leukocytopenia (43.2%) and alopecia (35.6%). Grade 3-4 diarrhoea, pain, oral and skin toxicity (4.4%, each) and nausea/vomiting, thrombocytopenia and elevated alkaline phosphatase (2.2%, each) were also reported. In 2 patients LVEF fell to <50%, with a decrease from baseline>15%. LVEF median values remained stable from baseline to the end of the study (60%). CONCLUSIONS: The combination of Myocet®, docetaxel and trastuzumab is safe and shows promising activity as first-line treatment of HER-2-positive MBC.

Scientific activity and needs among medical oncology units in sicily: a survey of the italian association of medical oncology.

In the era of targeted therapies and combined modalities of treatment, scientific research plays a role of paramount importance in improving knowledge of cancer treatment. The aim of this survey was to review the scientific activity of medical oncology units in Sicily and to analyze their needs and possible pitfalls in order to improve future scientific cooperation.The regional section of the Italian Association of medical Oncology (AIOM) approved this survey in November, 2007. A systematic review of scientific activity produced by medical oncology units in Sicily during the last 5 years has been reviewed. papers dealing with solid tumors reported in the pubmed web site have been included in the analysis. Data were reported as absolute number of published papers and impact factor per medical oncology unit and also as a ratio between global impact factor and the number of personnel working in each single unit to analyze scientific production according to the workforce of each institution.We identified a total of 283 papers reported in pubmed between 2004 and march, 2009. The mean number of publications/unit was 10.9 with a range of 0-50. The mean number of publications/year was 11.7 with a range of 0.2-10. The 15 units included in the impact factor evaluation published 252 papers with a total impact factor of 1014.6 points in 5 years with a mean of 63.4 points per institution and a mean of 4.02 points/paper. However only four medical oncology units reported a cumulative 5-year impact factor >100 points.This survey has shown that a minority of medical oncology units in Sicily is constantly involved in clinical research although at different levels of activity. Overall the percentage of patients enrolled in clinical trials is very low. The main reasons for lack of participation in clinical trials include insufficient medical personnel, the absence of a specifically dedicated research unit inside the medical oncology structures and in some cases lack of research experience and of specific interests in this field.

Capecitabine in combination with oxaliplatin or irinotecan in elderly patients with advanced colorectal cancer: results of a randomized phase II study.

BACKGROUND: To determine the efficacy and tolerability of capecitabine combined with oxaliplatin (CAPOX) or irinotecan (CAPIRI) as first-line treatment in patients with advanced/metastatic colorectal cancer aged > or =70 years. PATIENTS AND METHODS: Patients aged > or =70 years were randomly assigned to receive CAPOX [oxaliplatin 65 mg/m(2) intravenously (i.v.) days 1 and 8 and capecitabine 1000 mg/m(2) orally b.i.d. days 1-14; q21d] or CAPIRI (irinotecan 80 mg/m(2) i.v. days 1 and 8 and capecitabine 1000 mg/m(2) orally b.i.d. days 1-14; q21d). The primary study end point was overall response rate (ORR). RESULTS: Ninety-four patients were enrolled. In an intent-to-treat analysis, 2 complete responses (CRs) and 16 partial responses (PRs) were reported with CAPOX (ORR 38%), and 2 CRs and 15 PRs with CAPIRI (ORR 36%; P = 0.831). Median time to progression was 8 months for CAPOX and 7 months for CAPIRI (P = 0.195), with median survival times of 19.3 months and 14.0 months (P = 0.165), respectively. Global health status was improved in 45% and in 21% of patients in the CAPOX and CAPIRI arms, respectively. The most common treatment-related grade 3-4 adverse events in CAPIRI versus CAPOX patients were diarrhea (32% versus 15%; P = 0.052) and neutropenia (23% versus 6%; P = 0.021). CONCLUSION: CAPOX and CAPIRI had similar efficacy in elderly patients, although CAPOX seemed to be better tolerated.

Second-line chemotherapy in advanced pancreatic carcinoma: a multicenter survey of the Gruppo Oncologico Italia Meridionale on the activity and safety of the FOLFOX4 regimen in clinical practice.

BACKGROUND: In daily clinical practice second-line chemotherapy (SLCT) is frequently given to patients with advanced pancreatic cancer failing gemcitabine-based first-line chemotherapy without solid scientific support. PATIENTS AND METHODS: A retrospective survey was carried out including 42 patients. Patients received standard FOLFOX4 regimen biweekly until progression or unacceptable toxicity. RESULTS: Six partial responses (14%) and 16 stabilizations (38%) were recorded for a tumor growth control rate of 57%. The median time to progression (TtP) was 4 months (range 1-7 months), and median overall survival (OS) was 6.7 months (range 2-9 months). A stabilization of performance status (PS) and a subjective improvement of cancer-related symptoms were recorded in 27 patients. CONCLUSIONS: Data presented in this paper support the use of FOLFOX4 regimen in the second-line treatment of adenocarcinoma of the pancreas patients. The use of SLCT, however, should be carefully proposed to patients with good PS or those who had a good response to first-line therapy.

Temozolomide as salvage treatment in primary brain lymphomas.

Methotrexate (MTX)-based chemotherapy extends survival in patients with primary brain lymphomas, but it is not clear whether multiagent chemotherapy is superior to MTX alone. Treatment options for patients with recurrent primary brain lymphoma are limited; there is no standard second-line chemotherapy. New chemotherapeutic agents with clear activity in brain lymphoma are needed for treatment of recurrent disease. We report the results of a phase II trial assessing activity of the alkylating agent temozolomide in immunocompetent patients with recurrent primary brain lymphomas, previously treated with high-dose MTX-containing chemotherapy and/or radiotherapy. A median of two courses (range 1-12) of temozolomide 150 mg m-2 day-1, for 5 days every 4 weeks was administered to 36 patients yielding nine complete and two partial responses (response rate: 31%; 95% confidence interval 16-46%). One-year survival was 31% (95% confidence interval 16-46%). Toxicity was negligible. We conclude that temozolomide is active in recurrent primary brain lymphomas and should further be evaluated in this disease, perhaps in combination with MTX as initial treatment.

Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas.

BACKGROUND: The aim of the study was to evaluate the safety and efficacy of the raltitrexed/5-fluorouracil/levofolinic acid combination regimen as first-line chemotherapy for elderly patients with advanced/metastatic colorectal cancer. PATIENTS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 2 mg/m(2) i.v. plus levofolinic acid and 5-fluorouracil according to the De Gramont' schedule given every 2 weeks as first-line chemotherapy. Patients were re-evaluated after six cycles and chemotherapy was continued up to tolerance or disease progression. RESULTS: Seventy patients aged >/=65 years were accrued from 11 centers between September 2001 and July 2002. According to the intention-to-treat analysis, the overall response rate was 35% (95% CI 29.5% to 40.5%) including one complete response (1%) and 24 partial responses (34%). Twenty patients (31%) showed a stabilization of disease for a tumor growth control rate of 64% (95% CI 57% to 71%). The median overall survival was 12.5 months and the median time to disease progression was 6.5 months. No toxic deaths or allergic reaction were recorded. Grade 4 toxicities were non-existent. The main hematological toxicity was grade 3 neutropenia, which occurred in 9% of patients, and grade 3 anemia in only one case, while no case of graded 3 thrombocytopenia was observed. Grade 3 non-hematological toxicities were asthenia (11%), transient increase of transaminases (10%) and diarrhea (4%). CONCLUSIONS: The results of this study suggest that the raltitrexed/5-fluorouracil/levolofinic acid combination is an effective and well tolerated regimen for the treatment of elderly patients with advanced colorectal cancer. Its ease of administration and patient's tolerance warrant further investigation over 5-fluorouracil/folinic acid regimens.

Vinorelbine and prednisone in frail elderly patients with intermediate-high grade non-Hodgkin's lymphomas.

BACKGROUND: Frail patients with non-Hodgkin's lymphoma (NHL) are generally excluded from clinical trials and not even treated. The aim of this study was to evaluate the efficacy and tolerability of vinorelbine and prednisone in frail elderly patients with NHL. PATIENTS AND METHODS: Thirty consecutive frail elderly patients were entered in a phase II study with vinorelbine 25 mg/m2 i.v. on days 1 and 8 and oral prednisone 30 mg total dose on days 1-8 for six cycles. Criteria of frailty were age > or =80 years, or age > or =70 years and three or more comorbidities of grade 3 or at least one comorbidity of grade 4 according to the Cumulative Illness Rating Scale (CIRS), or not self-sufficient or the presence of one or more geriatric syndromes. RESULTS: Of 30 evaluable patients, three (10.0%) achieved a complete response (CR), nine (30.0%) showed a partial response (PR), while 10 presented with stable disease and eight with progressive disease. The median duration of CR was 29 months (range 5-36 months), and the median duration of PR was 1 month (range 1-22 months). Three patients had grade 3 neutropenia and one had grade 4. One grade 4 neurotoxicity was observed. Three patients died because of heart failure within 28 days of therapy, and one patient died after 4 days because of rapid progression. The median overall survival was only 10 months. CONCLUSION: Vinorelbine and prednisone is a relatively non-toxic combination with modest activity in frail patients with NHL. If initial aggressive chemotherapy has been excluded, this combination could be tried to obtain a temporary palliation.

Metastasis to the thyroid gland: a case report and review of the literature.

Metastatic cancer to the thyroid is uncommon. Although the thyroid is richly supplied with blood, there are a few reports of metastatic cancer spreading to this gland. The overall incidence in autopsy series has been quite varied, with rates from 1.2 to 24% of malignant tumors. Most of this metastases are not detected in clinical practice. The majority of these patients had widespread metastases and, as a result, had very short survival times. Although detection of metastases to the thyroid gland often indicates poor prognosis, aggressive surgical and medical treatment may be effective, especially for renal carcinoma. In this report, we present a case of renal carcinoma with thyroid metastases and a review of the literature.

[Medullary carcinoma of the thyroid: diagnosis and therapy]. / Il carcinoma midollare della tiroide: diagnosi e terapia.

Medullary thyroid carcinoma (MTC) originates in the thyroid C cells, or parafollicular cells, secreting calcitonin. It may be either sporadic or familial. Familial form can be isolated or expression of a multiple endocrine neoplasia type II. Mutations of the RET proto-oncogene have been identified in the germline DNA of patients with familial MTC syndromes. Genetic testing can identify patients affected by multiple endocrine neoplasia and familial MTC, allowing early diagnosis and possible cure. The initial treatment is surgical and the adequate surgery consists of total thyroidectomy. The treatment of occult or minimal disease can be curative. Plasma calcitonin measurements are excellent markers for post-operative follow-up. Imaging study can help to discover recurrent or metastatic disease. Adjunctive therapy includes radiotherapy and chemotherapy. Radiotherapy is reserved for bone metastases or for non resectable neck recurrences. Chemotherapy is reserved for patients with progressive MTC. Many chemotherapeutic regimens have been tried, results are controversial.

Fludarabine phosphate as an active and well tolerated salvage therapy in an elderly heavily pretreated Hodgkin's disease patient: a case report.

Up to two thirds of all patients affected by advanced Hodgkin's disease will be cured by chemotherapy alone or by combined chemoradiation modalities. High-dose chemotherapy with autologous stem cell rescue may be potentially curative for patients progressing under frontline chemotherapy or developing early relapse of disease. In spite of this, an unacceptably high percentage of these high-risk patients will relapse after salvage treatments and die of their disease. Fludarabine phosphate is an adenosine nucleoside analog highly active in chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphomas. There are only few data in the literature concerning its use in the management of Hodgkin's disease. We report the case of an elderly, heavily pretreated Hodgkin's disease patient in progression under third-line chemotherapy who experienced good palliation of her B symptoms and a major clinical response of her refractory bone lesions with the administration of fludarabine as monotherapy. The treatment was well tolerated, without grade 4 hematological toxicity or opportunistic infections. The duration of clinical remission and systemic symptom palliation was 9 and 11 months, respectively. Further evaluation of fludarabine phosphate as salvage therapy in relapsed/refractory elderly Hodgkin's disease patients is needed.

Treatment of multiple myeloma and acute myelogenous leukemia in the elderly: an update.

The optimal management of hematopoietic malignancies in the elderly requires the development of specific therapeutic strategies based on the peculiar clinico-biologic features of aged patients. Multiple myeloma arising in elderly patients remains at this time an incurable disease, while attention to supportive therapy and palliation can make a great impact on the quality of life. Fortunately advances have been made in last years in this field. Therapy at the time of diagnosis is usually recommended for patients with symptomatic disease, or for those who may be asymptomatic, but have evidence of high tumor burden of a biologically aggressive disease, and may be expected to progress and develop complications over a short period of time. Melphalan combined with prednisone remains the standard therapy choice in elderly patients. Radiotherapy maintains an important place in the palliation of destructive bone disease in poorly controlled myeloma, particularly in elderly patients. In Acute Myelogenous Leukemia, age has been concordantly reported as an adverse prognostic indicator in affecting both remission rates and survival. The overall unsatisfactory therapeutic results appear connected with host-related factors, and intrinsic differences in the biology of leukemia. Patients with standard risk should be included in collaborative trials aimed at improving the long-term results of conventional therapy. Patients with high risk and unfavorable prognostic factors, could be enrolled in controlled studies aimed at better assessing, in the elderly, the long term results of newer drug combinations. A watch and wait strategy, consisting of transfusion support and leukocytosis control, should be limited to patients with extremely poor performance status (PS), very limited life-expectancy and/or severe comorbidity displaying unfavorable biologic factors, including secondary Acute Myelogenous Leukemia.