Miklos Auber

5-Hydroxyindoleacetic acid and substance P profiles in patients receiving emetogenic chemotherapy.

Background. Even though direct cause and effect has not been proved, clinical evidence suggests serotonin and substance P (SP) are involved in the emetic response following chemotherapy. Because of several parallels, we hypothesized that SP release, like serotonin, may be propagated by chemotherapy and both substances can be measured in biological fluids, and correlated with a particular phase of emesis. Methods. Urinary 5-hydroxyindoleacetic acid (5-HIAA) was assessed by HPLC; serum and urine SP were measured by immunoassay. In addition to construction of neurotransmitter profiles, all SP data were grouped according to cisplatin dosages, = or>75 mg/m 2 versus <75 mg/m2, and phase of emesis, acute versus delayed. Analyses of these data were performed by repeated measures analysis of variance. Results. Samples were collected over a 72-hour period from 26 adult patients who received cisplatin-(n=13) or non-cisplatin-containing (n=13) chemotherapy. Mean baseline 5-HIAA: creatinine ratios were 5.23 and 5.16 in females and males, respectively; mean baseline SP levels were 392 and 181 pg/mL in females and males, respectively. Comparisons between SP data stratified by cisplatin dosage and emetic phase were significantly different, P <0.0001. Conclusions. Laboratory studies provide additional evidence that serotonin and SP are involved primarily, though not exclusively, in acute and delayed vomiting, respectively.

Priorities and uncertainties of administering chemotherapy in a pregnant woman with newly diagnosed colorectal cancer

Background. The absence of treatment standards for the use of chemotherapy in pregnancy is due, in part, to the fact that cancer in the gravid female is relatively uncommon. Method. A case (of a pregnant woman with newly diagnosed colorectal cancer) is presented to explore this area of medical uncertainty. Result. Managed by a multi-disciplinary team, successful prolongation of gestation was achieved with an oxaliplatin-based chemotherapy regimen. Conclusion. A perspective of the ongoing conflict between prolonging the mothers life and preserving fetal development is highlighted. Although not life-saving, administration of chemotherapy in this woman was life-sparing. J Oncol Pharm Practice (2009) 15: 5—8.

Cimetidine therapy of herpes simplex virus infections in immunocompromised patients

Five severely immunocompromised patients with progressive mucocutaneous manifestations of culture‐proven herpes simplex virus infection were treated with cimetidine—1200 mg per day by mouth (four patients) or by i.v. infusion (one patient). Treatment resulted in rapid improvement as evidenced by decreased local pain and crusting of lesions within 24–48 h. Complete resolution was observed within 3–13 days. These encouraging, albeit preliminary, findings suggest that cimetidine warrants further, large‐scale trials in patients with herpes virus infections.

High-Dose Therapy and Autologous Stem Cell Transplantation in Relapsed and Refractory Hodgkin’s Disease: Outcome Based on a Prognostic Model

We evaluated the results of high-dose therapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with relapsed or primary refractory Hodgkin’s disease (HD), using a previously reported prognostic model based on the presence of three poor prognostic factors at the start of salvage therapy/preparative regimen: B symptoms, extranodal disease and the duration of last complete response of less than 1 year. Based on this model, the patients were divided into low-risk and high-risk groups. Between 1993 and 2001, 24 patients with HD were treated with HDT and ASCT. Eighteen of the 24 patients had 0–1 risk factors (low-risk group) and 6 patients had 2–3 risk factors (high-risk group). Using Kaplan-Meier analysis, after a median follow-up of 40.5 months, the progression-free survival (PFS) was 48%, and the overall survival (OS) was 55%. PFS in the low-risk group was 56%, and in the high-risk group 17% (p < 0.001). OS in the low-risk group was 68% and in the high-risk group it was 18% (p < 0.001). The 100-day transplant-related mortality for the entire group was 16%. Our results are comparable to those reported in previous clinical trials for patients with refractory and relapsed HD treated with HDT and ASCT. The use of a prognostic model appears useful for predicting the outcome of HDT and ASCT for HD patients, and may play an important role in choosing the appropriate therapy for these patients.

Elevation of the Erythrocyte Sedimentation Rate Precedes Exacerbation of Bleomycin‐Induced Pulmonary Toxicity: Report of Two Cases and Review of Literature

Bleomycin is included in a number of potentially curative chemotherapy regimens. It is associated with distinct forms of pulmonary toxicity, with interstitial pneumonitis the most common. Early detection of pulmonary toxicity is not always predictable by monitoring serial chest radiographs and pulmonary function tests. Even newer serum markers are not useful indicators of bleomycin‐induced pulmonary damage. Two patients developed bleomycin pulmonary toxicity, in both of whom increases in erythrocyte sedimentation rate (ESR) preceded clinical deterioration and radiographic changes. The ESR may have potential significance as a monitoring test in patients receiving bleomycin.

Locally advanced rectal cancer with a pelvic kidney complicating adjuvant radiation therapy

The simultaneous occurrence of colorectal malignancy with pelvic kidney is unusual. We report a case of locally advanced rectal cancer stage III disease, T3N2M0, with a pelvic kidney complicating adjuvant radiation therapy. We recommend preoperative evaluation of the pelvic kidney to allow for its protection by translocation or heterotopic autologous transplantation. Occasionally a nephrectomy may be necessary. Otherwise extended lymph node dissection is not performed; hence, adequate treatment of the primary rectal cancer is compromised. The sequela of inadequate surgical excision and suboptimal radiation therapy is early relapse.

Efficacy of solubilized vemurafenib administered via nasogastric tube

Until only a few years ago, there was only one truly effective therapy for patients with metastatic melanoma. While long-term remission could be achieved in some patients, toxicities associated with high-dose IL-2 were significant. New insight related to molecular pathways of tumor cells indicated that an activating mutation of BRAF can be found in approximately 50-60% of all patients with melanoma. Proof-of-concept demonstrated in clinical trials of a drug targeting mutant BRAF led to the approval of vemurafenib by the US FDA in August 2011. Supplied in an oral dosage form, we provide an alternative method of administering vemurafenib in a patient unable to take anything by mouth.

Biological and clinical correlates after chemotherapy and granulocyte colony-stimulating factor administration.

Study Objective. To evaluate specific biological markers to improve understanding and use of granulocyte colony‐stimulating factor (G‐CSF) in patients receiving chemotherapy.