Michela Quirino

Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line

Objectives:  Although emerging data suggest that zoledronic acid (Zol) may have different anti‐tumour activities against a broad range of cancers, its effects on lung cancer remain largely unknown. The aim of this study was to evaluate in vitro the anti‐tumoural and anti‐angiogenetic effect of zoledronic acid in non‐small‐cell lung cancer (NSCLC) cells.

Nevirapine restores androgen signaling in hormone-refractory human prostate carcinoma cells both in vitro and in vivo.

Prostate carcinomas are androgen‐dependent neoplasms which progress toward a hormone‐independent phenotype during hormone‐deprivation therapy. We evaluated nevirapine, a reverse transcriptase inhibitor, as a new treatment in hormone‐refractory prostate carcinoma cells with the aim of restoring the androgen‐dependency of tumor cells, the rationale being that endogenous reverse transcriptase is up‐regulated in transformed cells and reverse transcriptase inhibitors exert a differentiating activity in human tumors.

A reversible coma after oxaliplatin administration suggests a pathogenetic role of electrolyte imbalance.

Sir, Oxaliplatin (OXA) is a third generation derivative of platinum compounds [1]. Unlike cisplatin and carboplatin, it is very effective in the treatment of colorectal cancer [2, 3]. Unfortunately, about 15% of patients treated with OXA gradually develop a dose-limiting severe chronic peripheral sensory neuropathy. Another less frequent neurotoxic manifestation is an acute type of peripheral neurotoxicity. Together, these side effects affect the overall efficacy of the treatment because they necessitate the interruption of OXA administration even in responding or potentially responding patients. The mechanism involved in OXA-linked neurotoxicity is still not well known, although the hypothesis that a product of OXA metabolic cleavage could interfere with the function of a peripheral nerve channel is generally accepted. Most authors agree that the voltage-gated sodium channels are involved [4, 5]. Case report

Unexpected side effect in mcrc: A care-compliant case report of regorafenib-induced hyperammonemic encephalopathy

Rationale: Regorafenib represents a treatment option in heavily pretreated patients affected by metastatic colorectal cancer (mCRC). Its safety profile is typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse events are manageable. Patient concerns: A 56 years-old Caucasian man affected by mCRC with normal hepatic reserve was treated with regorafenib as second-line treatment. After only 2 days of therapy, the patient presented to the emergency department due to impairment of both spatial and temporal orientation and motor function with bradylalia. Interventions: Serum ammonia level was 191 mmol/L, liver function tests and complete blood count were normal. Regorafenib was withheld and branched chain amino acids and lactulose were administered. Outcomes: Serum ammonia level returned within the normal range, but when regorafenib was restarted at a lower dose level, a new episode of acute confusion arised. Main lesson: Discontinuation of regorafenib after confirmation of hyperammonemia is strongly recommended; reintroduction of the therapy at lower doses after resolution of symptoms related to hyperammonemic encephalopathy has to be discouraged.

Cisplatin, dacarbazine and vinblastine as first line chemotherapy for liver metastatic uveal melanoma in the era of immunotherapy: a single institution phase II study

No standard therapy is established for metastatic uveal melanoma. Liver involvement in uveal melanoma may lead to organ impairment, which represents a common cause of death. Tumor shrinkage might improve survival by delaying hepatic failure. Since the combination of cisplatin, vinblastine, dacarbazine allowed a high response rate in metastatic cutaneous melanoma, we explored efficacy and safety of this regimen in unresectable liver metastases of uveal melanoma. In the present phase II study we administered intravenously cisplatin (80 mg/mq, day 1), dacarbazine (250 mg/mq/day, days 1–3), vinblastine (2 mg maximum, day 1) every 21 days as first line treatment for patients with unresectable metastases of uveal melanoma and BRAF wild type. Primary endpoint was objective response rate; overall survival (OS), progression-free survival and toxicity were secondary endpoints. Partial responses were observed in five (20%) patients, stable disease in 12 (48%) patients; disease control rate was 68%. Median OS of all the patients was 13 months, median progression free survival was 5.5 months. OS of responding patients was 21 months; OS of patients with disease control was 18 months, significantly longer than survival of progressing patients (7 months, P=0.0003). Five (20%) patients experienced grade 3–4 toxicity. Combination of cisplatin, vinblastine and dacarbazine was feasible and demonstrate both an interesting objective response rate and a survival benefit for patients achieving a disease control. This regimen could be considered for patients with good performance status and unresectable liver limited disease.

Is surgery mandatory in locally advanced gastrointestinal stromal tumors after imatinib? A case report and literature review

Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment.

Gastrointestinal stromal tumors (GISTs) and second malignancies A novel sentinel tumor? A monoinstitutional, STROBE-compliant observational analysis

AbstractSeveral evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis.A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-&agr; genes was performed in all patients. Following the involvement of KRAS mutation in many tumors’ pathogenesis, analysis of KRAS was performed in patients with also second neoplasms.Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-&agr; mutation (n. 2) and exon 18 PDGFR-&agr; mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months.The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis.