Role of Chemotherapy in Vulvar Cancers: Time to Rethink Standard of Care?

The actual role of chemotherapy in vulvar cancer is undeniably a niche topic. The low incidence of the disease limits the feasibility of randomized trials. Decision making is thus oriented by clinical and pathological features, whose relevance is generally weighted against evidence from observational studies and clinical practice. The therapeutic management of vulvar cancer is increasingly codified and refined at an individual patient level. It is of note that the attitude towards evidence sharing and discussion within a multidisciplinary frame is progressively consolidating. Viable options included in the therapeutic armamentarium available for vulvar cancer patients are frequently an adaption from standards used for cervical or anal carcinoma. Chemotherapy is more frequently combined with radiotherapy as neo-/adjuvant or definitive treatment. Drugs commonly used are platinum derivative, 5-fluorouracil and mitomicin C, mostly in combination with radiotherapy for radiosensitization. Exclusive chemotherapy in the neo-/adjuvant setting comprises platinum-derivative, combined with bleomicin and methotrexate, 5-fluorouracil, ifosfamide or taxanes. In advanced disease, current regimens include cisplatin-based chemoradiation, with or without 5-fluorouracil, or doublets with platinum in combination with a taxane. Our work is also enriched by a concise excursus on the biologic pathways underlying vulvar cancer. Introductory hints are also provided on targeted agents, a rapidly evolving research field.

Digital Ischemia and Necrosis from Oxaliplatin

Oxaliplatin is a chemotherapeutic agent used in a variety of malignancies such as colorectal cancer and pancreatic cancer. It is a platinum derivative that results in direct cell cytotoxicity with resultant cell death. The most common side effects often noted are neurotoxicity, nausea, vomiting, diarrhea, hepatotoxicity and myelosuppression. Oxaliplatin induced digital ischemia and necrosis is a rare side effect that was observed in our patient. In general, digital ischemia is a rare vascular disorder that is often associated with autoimmune disease [1]. Here, we intend to present a patient with digital ischemia due to Oxaliplatin, which was a chemotherapy agent used in the treatment of his urachal adenocarcinoma.

Zingiber officinale Roscoe Rhizomes Attenuate Oxaliplatin-Induced Neuropathic Pain in Mice

Oxaliplatin is a platinum derivative chemotherapeutic drug widely used against cancers, but even a single treatment can induce a severe allodynia that requires treatment interruption and dose diminution. The rhizome of Zingiber officinale roscoe (Z. officinale, ginger), has been widely used in traditional medicine to treat various diseases causing pain; however, its effect against oxaliplatin-induced neuropathic pain has never been assessed. In mice, a single oxaliplatin (6 mg/kg, i.p.) treatment induced significant cold and mechanical allodynia. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. Water extracts of Z. officinale (100, 300, and 500 mg/kg, p.o.) significantly attenuated both cold and mechanical allodynia induced by oxaliplatin. Intrathecal pre-treatment with the antagonist 5-HT1A (NAN-190, i.t., 1 μg), but not with the antagonist 5-HT2A (ketanserin, i.t., 1 μg), significantly blocked the analgesic effect of Z. officinale against both cold and mechanical allodynia. However, 5-HT3 antagonist (MDL-72222, i.t., 15 μg) administration only blocked the anti-allodynic effect of Z. officinale against cold allodynia. Real-time PCR analysis demonstrated that Z. officinale significantly increased the mRNA expression of the spinal 5-HT1A receptor that was downregulated after oxaliplatin injection. These results suggest that Z. officinale may be a viable treatment option for oxaliplatin-induced neuropathic pain.

Oxaliplatin induced laryngospasm: a case series

Oxaliplatin is a third-generation platinum derivative used as a first-line agent in the treatment of colorectal carcinoma, biliary tract cancer and gastric cancers and can be used as a neoadjuvant/adjuvant in these cancers. The dose limiting toxicity is peripheral neuropathy, others include hypersensitivity reactions, haematological toxicity and pulmonary fibrosis. Hypersensitivity reactions can extend from milder reactions like urticaria, rash to severe symptoms like hypotension and laryngospasm. The laryngospasm due to oxaliplatin is reported to be reversible with corticosteroids, antihistamines and oxygen. This case series suggest that oxaliplatin has a propensity to cause severe hypersensitivity reaction presenting as laryngospasm not with a single dose but with subsequent doses of oxaliplatin. Prompt symptomatic treatment with corticosteroids leads to reversal of symptoms and improvement in the condition of the patient.

Platinum Derivatives Effects on Anticancer Immune Response

Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells’ fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints’ expression.

Case Report: Oxaliplatin-Induced Immune-Mediated Thrombocytopenia

Thrombocytopenia is a frequent complication of cancer may be due to a variety of causes including malignancy itself, acute disease processes, or cancer therapy. Systemic cancer therapy is the most common cause of thrombocytopenia in cancer patients observed nearly two-thirds of patients with solid tumors. Thrombocytopenia with traditional chemotherapy agents is most frequently the result of megakaryocyte cytotoxicity. Oxaliplatin is a platinum derivative commonly used in gastrointestinal malignancies and is associated with drug-induced immune thrombocytopenia.

Audiological Monitoring in Children Treated with Platinum Chemotherapy

Platinum compounds constitute the standard treatment for solid tumors in pediatric oncology. The purpose of this study is to assess the impact of platinum compounds in the development of ototoxicity in children following chemotherapy. This study included 160 patients treated with cisplatin and carboplatin for malignant solid diseases from 2007 to 2014. Their audiograms were classified according to the Boston SIOP ototoxicity scale. Twenty-five percent of the children treated with platinum compounds developed ototoxicity. The incidence of ototoxicity was correlated with the type of platinum derivative (i.e. cisplatin vs. carboplatin), coadministration of both drugs and concomitant cranial radiotherapy, but not with sex and age. Cumulative dose was correlated only with the cisplatin administration. Nine patients (8.6%) showed further progression of hearing impairment after the end of chemotherapy. The low rate of ototoxicity suggests the pivotal role of auditory monitoring in children treated with platinum compounds in order to be able to identify hearing loss at an early stage and to provide, jointly with pediatric oncologists, strategies to reduce further progression of cochlear toxicity.

Visualizing soaking process of protein crystal

Time-resolved visualization of the soaking process of tetragonal lysozyme crystal was performed by synchrotron radiation microtomography. Mother liquor containing hexachloroplatinate was introduced into a capillary bearing lysozyme crystals to visualize crystals undergoing soaking. The platinum distribution was first observed in the superficial layer of crystal and then gradually penetrated into the crystal core. The crystal structure of the platinum derivative in each soaking period was determined by time-resolved crystallography. A total of five platinum sites were identified in Bijvoet difference maps. These sites were classified into two groups on the basis of the time dependence of electron density development. A soaking process model consisting of binding-rate-driven and equilibrium-driven layers is proposed to describe the results. This study suggests that the structures of soaked crystals vary depending on the crystal position from which diffractions were taken.