Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

Basal cell carcinomas (BCCs) were essentially a molecular 'black box' until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours.

/pdf/basal-cell-carcinomas-attack-of-the-hedgehog-4wxo5xy87f.pdf

Basal cell carcinomas: attack of the hedgehog

Objective To review preclinical and clinical data for oxaliplatin in the current context of molecularly targeted therapy. Methods of Study Selection We searched the PubMed and PubChem databases by combining the search terms "oxaliplatin" or "platinum" or both, with "clinical trials," "pharmacokinetics," and "pharmacodynamics." Data Extraction and Synthesis Oxaliplatin has a complicated pharmacokinetic profile, with activity against digestive cancers in particular. It has several mechanisms of action, but cancer cells can develop resistance. Real or potential synergism has been observed when oxaliplatin is combined with other cytotoxic agents or molecularly targeted agents. Peripheral neuropathy is a prominent toxic effect. Conclusions Oxaliplatin lends itself to further clinical research in combination with molecularly targeted therapy.

https://www.mdpi.com/1718-7729/18/1/708/pdf

Oxaliplatin: a review in the era of molecularly targeted therapy

The immune system deploys a multitude of innate and adaptive mechanisms not only to ward off pathogens but also to prevent malignant transformation ("immune surveillance"). Hence, a clinically apparent tumor already reflects selection for those malignant cell clones capable of evading immune recognition ("immune evasion"). Metal drugs, besides their well-investigated cytotoxic anticancer effects, massively interact with the cancer-immune interface and can reverse important aspects of immune evasion. This topic has recently gained intense attention based on combination approaches with anticancer immunotherapy (e.g., immune checkpoint inhibitors), a strategy recently delivering first exciting results in clinical settings. This review summarizes the promising but still extremely fragmentary knowledge on the interplay of metal drugs with the fidelity of anticancer immune responses but also their role in adverse effects. It highlights that, at least in some cases, metal drugs can induce long-lasting anticancer immune responses. Important steps in this process comprise altered visibility and susceptibility of cancer cells toward innate and adaptive immunity, as well as direct impacts on immune cell populations and the tumor microenvironment. On the basis of the gathered information, we suggest initiating joint multidisciplinary programs to implement comprehensive immune analyses into strategies to develop novel and smart anticancer metal compounds.

Metal Drugs and the Anticancer Immune Response.

/pdf/basal-cell-and-squamous-cell-skin-cancers-m1ppvrw62f.pdf

Basal cell and squamous cell skin cancers.

Basal cell carcinoma (BCC) is usually a benign and indolent cancer cured in greater than 95 percent of cases. Nevertheless, it can be locally destructive or occasionally metastasize to distant organs. We report a case of BCC metastatic to the lungs, occurring 17 years after the primary BCC was noticed, that responded to carboplatin and paclitaxel on 3 occasions. The patient also developed pure red cell aplasia (PRCA). Work-up did not reveal underlying thymoma or infectious, rheumatologic, or lymphoproliferative disorders. Parvovirus serologies were negative, and antibodies against erythropoetin were not detected. There was no history of exposure to drugs associated with PRCA. Bone marrow biopsy on 2 different occasions did not show evidence of myelodysplasia. PRCA may represent an unusual paraneoplastic syndrome associated with BCC as reported with other carcinomas. This is the first report of PRCA associated with metastatic BCC or the drugs carboplatin and paclitaxel, which were used to treat it. The literature on chemotherapy for metastatic BCC is reviewed.

Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia.

A 56-year-old woman diagnosed with a poorly differentiated cecal adenocarcinoma with metastases to ovaries, omentum, and sigmoid colon went into remission after 12 cycles of infusional 5-fluorouracil, luecovorin, and oxaliplatin (FOLFOX-4 regimen). Thirteen months later, a pelvic recurrence was diagnosed, and the patient received nine cycles of FOLFOX-6 plus bevacizumab, resulting in a clinical complete response but the development of pancytopenia. Bone marrow biopsy was consistent with therapy-related acute myelogenous leukemia. Chromosome analysis showed structural rearrangements with partial deletions of the long arms of chromosomes 5, 7, 20, and 21, as well as trisomy of chromosome 8 and losses of chromosomes 3 and 11. Induction chemotherapy led to remission, but the patient died two months later from complications of colon cancer progression. It is likely that the leukemia was related to the oxaliplatin administration.

https://theoncologist.onlinelibrary.wiley.com/doi/pdf/10.1634/theoncologist.11-3-261

Oxaliplatin-related acute myelogenous leukemia

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of gemcitabine using a fixed dose rate infusion (FDRI) in combination with gefitinib in patients (pts) with pancreatic adenocarcinoma (PCa). Patients and methods: Patients with advanced PCa were given gemcitabine at the FDRI of 10 mg/m2/min IV on Days 1, 8, and 15 of a 28-day cycle. Dose levels of 1000, 1200, and 1500 mg/m2 were evaluated. Oral gefitinib 250 mg was given daily. DLTs were defined as 2 instances of Grade 3 hematologic or 4 nonhematologic or any Grade 4 hematologic toxicity. At least 4 patients were treated at each dose level. Dose escalation occurred in the absence of DLTs. Results: Five women and 8 men were enrolled. Median age was 59 and performance status 1. All had metastatic disease. Four patients received prior adjuvant chemoradiation for PCa, and one chemotherapy for lung cancer. Median cycles were 4 per patient. The MTD was 1,200 mg/m2. Toxicity was predominantly hematologic. At 1,500 mg/m2, 1...

Phase I Trial of Fixed Dose Rate Infusion Gemcitabine with Gefitinib in Patients with Pancreatic Carcinoma

4118 Background: Patients (pts) with metastatic pancreatic adenocarcinoma (PCa) treated with GEM using a FDRI have a longer survival than with 30 min infusion schedules1. Over 40% of metastatic PCa’s overexpress EGFR2. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of GEM using a FDRI in combination with gefitinib, an EGFR TK inhibitor in pts with PCa. Methods: Pts with advanced pancreatic cancer were given GEM at the FDRI of 10 mg/m2/min IV on days 1, 8, and 15 of a 28 day cycle. Dose levels of 1000, 1200 and 1500 mg/m2 were evaluated. Oral gefitinib 250 mg was given daily. DLTs were defined as two instances of grade III hematologic or IV non-hematologic toxicity or any grade IV hematologic toxicity. Four pts were treated at each dose level. Dose level escalation occurred in the absence of DLTs. Results: Four women and 8 men were enrolled. Median age was 61. All pts were PS 0 or 1 and had metastatic disease (83.3% liver; 16.6% lungs). Three pts received...

Phase I trial of fixed dose rate infusion (FDRI) gemcitabine (GEM) with gefitinib in patients with advanced pancreatic carcinoma

The development of molecular biology tools has led to the identification of numerous therapeutic targets in cancer cells. In this article, we discuss the rational and clinical data supporting the use of agents that selectively target epidermal and vascular endothelial growth factors in selected cancers.

Benedito A. Carneiro

Papers

Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia.

Oxaliplatin-related acute myelogenous leukemia

Phase I Trial of Fixed Dose Rate Infusion Gemcitabine with Gefitinib in Patients with Pancreatic Carcinoma

Phase I trial of fixed dose rate infusion (FDRI) gemcitabine (GEM) with gefitinib in patients with advanced pancreatic carcinoma

Evolving molecular-based targeted therapy for cancer: an exciting field.