Liliana Montella

Early Skin Toxicity as a Predictive Factor for Tumor Control in Hepatocellular Carcinoma Patients Treated with Sorafenib

INTRODUCTION Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients. MATERIALS AND METHODS All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand-foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response plus stable disease) and TTP. RESULTS Sixty-five HCC patients treated with sorafenib were included in this analysis: 47 (73.3%) received sorafenib after failure of some local treatment, whereas 18 (27.7%) received it as first-line treatment. Twenty-nine patients developed at least grade 1 skin toxicity (rash, 13; HFSR, 16). In patients who developed skin toxicity, the tumor control rate was 48.3%, versus 19.4% in patients without cutaneous side effects. The median TTP was 8.1 months in the group of patients with skin toxicity versus 4.0 months in those without skin toxicity. This difference was also statistically significant on multivariate analysis. A borderline statistically significant difference was also observed in terms of OS in patients with early skin toxicity. CONCLUSIONS Skin toxicity should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy.

Phase 2 Trial of Temozolomide Using Protracted Low-dose and Whole-brain Radiotherapy for Nonsmall Cell Lung Cancer and Breast Cancer Patients With Brain Metastases

Temozolomide (TMZ), an oral methylating imidazotetrazinone, has antitumor activity against gliomas, malignant melanomas, and brain metastasis and is presently administered as a 5‐day oral schedule every 4 weeks.

Randomized Phase III Trial on Gemcitabine Versus Mytomicin in Recurrent Superficial Bladder Cancer: Evaluation of Efficacy and Tolerance

PURPOSE Approximately 30% to 40% patients with a superficial bladder cancer treated with Bacille Calmette-Guerin (BCG) or epirubicin do not respond; of the initial responders, 35% have a relapse within 5 years. We compare the therapeutic efficacy and toxicity of intravescical infusions of gemcitabine (GEM) with mitomycin (MMC) in patients with a recurrent superficial bladder cancer. PATIENTS AND METHODS Patients with a history of a previously treated, recurrent Ta-T1, G1-G3 bladder transitional cell carcinoma were enrolled in the study. The patients received a 6-week course of GEM infusions or 4-week course of MMC. In both arms, for the initial responders who remained free of recurrences, maintenance therapy consisted of 10 monthly treatments during the first year. RESULTS A total of 120 patients were enrolled and randomly assigned to either the MMC or GEM treatment arm. At the end of the study, 109 patients (55 in MMC and 54 in GEM) were assessable. The median duration of follow-up was 36 months for either arm. In the GEM arm, 39 (72%) of 54 patients remained free of recurrence versus 33 (61%) of 55 in MMC arm. Among patients with recurrences, 10 in the MMC arm and six in the GEM arm also had a progressive disease by stage. The incidence of chemical cystitis in the MMC arm was statistically higher than in the GEM arm (P = .012). CONCLUSION This study demonstrates that GEM has better efficacy and lower toxicity than MMC; therefore, GEM appears as a logical candidate for intrabladder therapy in patients with refractory transitional cancer.

Low-Dose Metronomic Oral Administration of Vinorelbine in the First-line Treatment of Elderly Patients With Metastatic Breast Cancer

BACKGROUND The concept of metronomic chronic administration of low-dose chemotherapy has become relevant for the treatment of cancer in the last several years. This study sought to determine the safety and activity of oral vinorelbine (VNB), using a metronomic schedule of administration, in elderly patients with metastatic breast cancer (MBC). PATIENTS AND METHODS From October 2004 to March 2007, 34 patients with MBC (median age, 74 years; range, 70-84 years) were treated with oral VNB at 70 mg/m2, fractionated on days 1, 3, and 5, for 3 weeks on and 1 week off, every 4 weeks, for a maximum of 12 cycles. The objective response rate was the primary endpoint. RESULTS All 34 patients received at least 3 cycles of therapy and were evaluable. Two achieved complete responses (6%), and 11 achieved partial responses (32%). Median progression-free survival and median overall survival entailed 7.7 months (95% confidence interval, 6.9-9.05 months) and 15.9 months (95% CI, 13.1-15.91 months), respectively, for all patients. CONCLUSION The fractionated administration of oral VNB is well tolerated and presents promising activity in elderly patients with metastatic cancer, warranting further investigation in combination with other chemotherapy agents.

Cetuximab is an active treatment of metastatic and chemorefractory thymoma

Advanced chemorefractory thymic epithelial tumors still represent a challenge in clinical oncology. A rationale-based therapeutic approach targeting a key pathway should represent the ideal solution in a neoplasm that can over-express Epidermal Growth Factor Receptor (EGFR) in the epithelial component. On the basis of these considerations, two patients with metastatic heavily pretreated disease were evaluated for EGFR expression in the primitive tumor, being considered this data as a basis for an anti EGFR treatment with the monoclonal antibody cetuximab which targets EGFR. A strong EGFR expression was revealed by immunohistochemistry in the two cases considered, thus the patients received cetuximab and reported a partial response as assessed by Computed Tomography (CT), Positron Emission Tomography (PET) and fused PET-CT after three months of therapy. Therefore, both patients are still on therapy. This preliminary experience suggests that cetuximab may be a useful therapeutic choice in advanced pre-treated thymic tumors.

Ultra-low-dose interleukin-2 in unresectable hepatocellular carcinoma

At present, no effective therapy is available for hepatocellular carcinoma, when local treatments have failed. We reported the results obtained with prolonged, ultra-low-dose (1 MIU/d until progression), subcutaneous interleukin-2 (IL-2) in a series of 18 consecutive patients (14 men and 4 women, median age 66 years, range 49–82 years) with advanced, histologically proven HCC on liver cirrhosis. During a median follow-up time of 19.5 months, two complete responses (11.1%), lasting 35 and 46 months, respectively, and one partial response (5.5%) were recorded (overall response rate: 16.6%; 95% CI: 0–33.8%). Thirteen patients (72.3%; 95% CI: 61.6–82.7) had stable disease lasting at least 4 months; 1 of these patients obtained a complete response on lung metastases. Median time to progression was 15.3 months (95% CI: 10–33). Median overall survival was 24.5 months (95% CI: 12–43). Two patients (11.1%) progressed during therapy. Toxicity was only local (usually pain and pomphus in the site of injection). Low-dose IL-2 can be considered an active and well-tolerated treatment for unresectable hepatocellular carcinoma. Future studies on large numbers of patients are necessary to confirm these results.

Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs)

BACKGROUND No previous prospective trials have been reported with capecitabine and gemcitabine (CAP-GEM) in patients with metastatic thymic epithelial tumors (TETs). We conducted a multicenter study to determine the activity and tolerability of this regimen in pretreated TETs. PATIENTS AND METHODS A total of 15 patients were enrolled in the first stage of phase II study. All patients received CAP-GEM every 3 weeks. The primary end point was objective response rate (RR); secondary end points were toxicity, progression-free survival (PFS) and overall survival. RESULTS Complete responses (CR) and partial responses were observed in three (20%) and three (20%) patients for a 40% RR, respectively. Grade 1-2 neutropenia, anemia and thrombocytopenia were the most common side-effects, noted in seven (46.7%), five (33.3%) and five (33.3%) patients, respectively. The most common grade 3 toxicity was neutropenia in three patients (20%). Median PFS was 11 months (95% confidence interval 4-17). The 1- and 2-year survival rates were 80% and 67%, respectively. CONCLUSION We have decided to publish the preliminary results because this regimen was more active than that expected. Although our results are preliminary, CAP-GEM shows activity and safety in pretreated TETs. Furthermore, multicenter trials, also in first-line setting, are necessary to confirm our results.

Sorafenib in elderly patients with advanced hepatocellular carcinoma: a case series.

Objective: The management of hepatocellular carcinoma (HCC) in elderly patients is significantly more complicated than in younger patients because of medical comorbidities, advanced status at diagnosis, reduced liver function and altered drug pharmacokinetics. Our objective was a revision of the charts of unselected elderly patients with HCC being treated with a reduced starting dose of sorafenib. Methods: Activity, adverse events and quality of life were evaluated during the treatment. Sixty patients (47 males and 13 females) aged more than 70 years old (range 70-90, median 76 years) were retrospectively reviewed. Results: One complete and one partial response were achieved in the series (overall response rate 3.3%). Stable disease accounted for 76.6% (46 out of 60 patients). The disease control rate (complete plus partial response plus stable disease) was 80%. Median time to progression (TTP) was 7.0 months (95% CI, 5.2-8.7 months) and median survival was 10.0 months (95% CI, 5.0-14.9 months). Thrombosis correlated to TTP. Full doses of sora-fenib were reached in 11 out of 60 patients (18.3%). The evaluation of quality of life did not show any significant change during the study. Conclusions: Sorafenib at a reduced dose can be safely used in elderly HCC patients with maintenance of activity and increased tolerability.

Zoledronic acid in treatment of bone lesions by Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a rare disease, probably an atypical myeloproliferative syndrome, with variable clinical presentation and behavior. In this report, we focus on bone involvement by LCH and treatment with zoledronic acid in six patients as they progressed after chemotherapy and radiotherapy. Zoledronic acid appeared safe and produced significant relief in pain.

Atrial fibrillation following chemotherapy for stage IIIE diffuse large B-cell gastric lymphoma in a patient with myotonic dystrophy (Steinert’s disease)

The authors describe the unusual association between diffuse B-cell gastric lymphoma and myotonic dystrophy, the most common form of adult muscular dystrophy, and sudden atrial fibrillation following one cycle of doxorubicin-based chemotherapy in the same patient. Atrial fibrillation or other cardiac arrhythmias are unusual complications in patients treated with chemotherapy. The cardiac toxicity intrinsically associated with the aggressive chemotherapy employed could function as a triggering factor for the arrhythmia in the predisposed myocardium of this patient.