Perianal basosquamous carcinoma treated with radiation therapy, a case report.

Background: Perianal basal cell carcinoma (BCC) is very rare and estimated to account for 0.08% of all BCC and 0.02% of all anorectal neoplasms. Perianal lesions are more likely to be squamous cell carcinoma (SCC) as BCC usually develops on areas of skin exposed to ultraviolet (UV) light such as the face and arms. Proper diagnosis with the assistance of immunohistochemistry (IHC) stains to distinguish the two entities can help inform the suitable course of treatment. Case Description: Our case is an 82-year-old male with a history of cutaneous BCC on the arms and trunk presenting with a symptomatic perianal lesion. Initial biopsy demonstrated BCC with subsequent IHC studies differentiating from basaloid SCC. Standard treatment includes wide local excision (WLE) but given his poor performance status, radiation only was recommended. He was successfully treated and tolerated 30 Gy in 5 daily fractions. Conclusions: Radiation only is a unique and feasible non-surgical treatment for basosquamous carcinoma of the anus.

Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma.

Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma.

Combined modality therapy for pancreatic cancer.

In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. According to several phase II trials and Gastrointestinal Tumor Study Group results, improvements in locoregional control and survival may be achieved when chemotherapy is added to radiation for locally advanced pancreatic cancer. Radiosensitizing chemotherapy agents such as 5-fluorouracil, gemcitabine, paclitaxel, and cisplatin have shown promise. Selected patients with locally advanced disease have been downstaged with chemoradiation, facilitating surgical resection. For patients with resectable disease, the completion of Radiation Therapy Oncology Group study 97-04 represents a major achievement and brings gemcitabine into the forefront of adjuvant therapy. Neoadjuvant chemoradiation may eliminate the delay of initiating adjuvant treatment and spare unnecessary surgery for patients with rapid systemic progression. Molecular agents are being combined with chemoradiation in an attempt to delay or prevent systemic progression.

Effects of Chinese herbal medicine in combination with mitomycin C on gastric cancer cells.

Chinese herbal medicine (CHM) is frequently used by cancer patients in Chinese community. It remains largely unknown about the interaction between CHM and chemotherapeutic agents. Herein, we evaluated 3 commonly used CHM formulas for cancer patients: Bu-Zhong-Yi-Qi-Tang (BZYQT), Bao-Yuan-Tang (BYT), and Ju-Yuan-Jian (JYJ). We examined the effects of these 3 formulas in human gastric cancer cells MKN-74, in terms of cytotoxicity and apoptosis induction when used alone or in combination with mitomycin C (MMC). Cytotoxicity was determined by tetrazolium dye colorimetric assay. The 10% inhibitory concentration of CHM was used in this study. Cells were first exposed to CHM or phosphate buffered saline (as control) for 48 h. Then MMC at final concentration of 0.25 µg/ml was added to media for another 24-h. Among these 3 CHM formulas, BZYQT showed the most pronounced effect in augmenting MMC-induced cytotoxicity. The viability of MKN-74 cells was decreased to 43.1% when treated with BZYQT and MMC, compared to 94.9% with MMC alone. We subsequently examined apoptosis induction by quantitative florescent microscopy and single-strand DNA enzyme-linked immunosorbent assay, and found BZYQT did not enhance MMC-induced apoptosis. Our findings indicate BZYQT in combination with MMC induces cell death in gastric cancer cells via non-apoptotic mechanism. Our results provide a rationale for further investigation in the interaction of CHM and anti-cancer treatment.

Phase I study of docetaxel, capecitabine, and carboplatin in metastatic esophagogastric cancer.

OBJECTIVES: A phase I trial was conducted to determine the maximally tolerated dose (MTD) and dose-limiting toxicities (DLTs) of docetaxel, capecitabine, and carboplatin for first-line treatment of patients with metastatic esophageal and gastric cancers. METHODS: Twenty-eight patients were treated over 5 dose levels in a 21-day cycle. Patients received carboplatin (AUC = 2) on days 1 and 8, docetaxel (35-40 mg/m2) on days 1 and 8, and capecitabine (500-2000 mg/m2) on days 1 to 10. RESULTS: There were no DLTs in the first cycle of treatment. Dose reductions were required in 10 of 15 patients at the final dose level due to neutropenia, nausea, vomiting, diarrhea, dehydration, and hand/foot syndrome following a median of 3 cycles of treatment. Therefore, escalation beyond dose level 5 was not attempted. The MTD was docetaxel, 40 mg/m2 days 1 and 8; carboplatin, AUC = 2 days 1 and 8; and capecitabine, 1500 to 2000 mg/m2 days 1 to 10 in a 21-day cycle. Ten of 25 patients who could be evaluated (40%) responded and 8 of 14 patients treated at the final dose level responded (57%). CONCLUSIONS: Cumulative gastrointestinal toxicities and neutropenia were the DLTs of docetaxel, capecitabine, and carboplatin. This combination represents an easily administered, active regimen for patients with metastatic gastric and esophageal cancers. Further evaluation of this regimen is indicated.

Status of treatment for advanced gastric carcinoma.

Gastric cancer is the second most common cause of cancer death worldwide. Advanced gastric cancer is incurable. The most widely investigated single-agent chemotherapy is 5-fluorouracil (5-FU), with partial response rates up to 20%. Pilot phase II studies investigating combinations of 5-FU, anthracyclines, mitomycin, methotrexate, and platinums achieved higher response rates; however, the response rates declined in subsequent larger trials. Furthermore, toxicity was substantially higher in confirmatory trials, emphasizing the need to develop well-tolerated regimens prior to multi-institutional testing. Although phase III studies of combination regimens have not achieved a clear worldwide standard, the regimen of epirubicin, cisplatin, and continuous-infusion 5-FU achieved a survival benefit, possibly through the increased activity of infusional 5-FU combined with cisplatin. The taxanes, irinotecan and oxaliplatin, have recently shown important activity in gastric cancer. Patient accrual to a phase III trial comparing a docetaxel-based combination regimen with the regimen of cisplatin and 5-FU has completed accrual. Whether patients with adenocarcinomas of the proximal stomach and gastroesophageal junction will have the same response rates to these new agents as did patients with classical body and distal gastric cancers is unknown. It is anticipated that the development of these active new agents will ultimately improve survival for patients with advanced gastric cancer.

Paclitaxel and concurrent radiation in upper gastrointestinal cancers.

Effective locoregional treatments are needed for adenocarcinomas of the esophagus, stomach, and pancreas. Paclitaxel has been investigated as a radiation sensitizer for upper gastrointestinal malignancies. In esophageal cancer, the combination of low-dose weekly paclitaxel, platinum, and concurrent radiation therapy (RT) has substantial activity and is well tolerated. Regimens that add fluorouracil (5-FU) to paclitaxel and platinum or incorporate hyperfractionation radiation have a higher incidence of severe esophagitis. In gastric cancer, adjuvant concurrent paclitaxel, 5-FU, and radiation is being investigated in the cooperative group setting. In pancreatic cancer, paclitaxel may be a radiation sensitizer even to tumor cells that are resistant to paclitaxel as a single agent. The Radiation Therapy Oncology Group (RTOG) demonstrated a 43% 1-year survival with paclitaxel/RT for patients with locally advanced pancreatic cancer. This represented a 40% improvement in survival compared to the previous RTOG 92-09 study of 5-FU-based chemoradiation. Ongoing trials in pancreatic cancer are investigating the addition of gemcitabine to paclitaxel and radiation and incorporating molecular targeting agents.

HER-2/neu and p53 in osteosarcoma: an immunohistochemical and fluorescence in situ hybridization analysis.

The overexpression of HER-2/neu and p53 has been associated with poor outcome in many neoplasms. Their role in patients with osteosarcoma is unclear. We studied the expression of HER-2/neu and p53 in 22 osteosarcoma samples (from 20 patients--2 had locally recurrent disease) biopsied at the University of Medicine and Dentistry of New Jersey (UMDNJ) from 1996-2000 using both immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Fourteen patients (14 samples) presented with Stage II and 6 patients (8 samples) presented with Stage III disease. Median follow-up is two years (range one year to five years). Four of 22 (18%) samples showed focal membranous or cytoplasmic positivity for HER-2/neu and six of 22 samples (27%) showed nuclear positivity for p53 by IHC analysis. In contrast, none of 22 tested samples showed gene amplification for HER-2/neu by FISH analysis. Seven of 13 HER-2/neu and p53 negative patients (54%) are currently disease free (between one year to five years). In this sample of patients, the HER-2/neu oncogene is not overexpressed or amplified in osteosarcoma; six of 22 samples (27%) showed overexpression of p53 by IHC analysis. By FISH, none of the samples demonstrated deletion of p53. Neither HER2/neu nor p53 expression was important for the biology of osteosarcoma in this population.

Trastuzumab, paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus: a phase I study.

PURPOSE: To conduct a phase I study incorporating trastuzumab with paclitaxel, cisplatin, and radiation for adenocarcinoma of the esophagus. METHODS AND MATERIALS: Patients with adenocarcinoma of the esophagus without distant organ metastases were eligible. All patients received cisplatin 25 mg/m2 and paclitaxel 50 mg/m2 weekly for 6 weeks with radiation 50.4 Gy. HER-2/neu-positive patients (2+/3+ by immunohistochemistry) received weekly trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg, respectively. HER-2/neu-negative patients received the same chemoradiation without trastuzumab as a control for toxicity. Dose-limiting toxicities were defined as grade 3 esophageal, cardiac, or pulmonary toxicity. RESULTS: Twelve of 36 screened patients (33%) overexpressed HER-2/neu by immunohistochemistry (seven 3+ and five 2+). Eight of 12 patients with HER-2/neu overexpression by IHC had an increase in the number of HER-2/neu genes, six from amplification of the HER-2/ neu gene and two were hypderdiploid for chromosome 17. Thirty patients were enrolled (12 HER-2/neu-positive and 18 HER-2/neu-negative controls). No increase in toxicity was seen with the addition of trastuzumab. One of 12 patients in the trastuzumab arm and 8 of 17 in the control arm had grade 3 esophagitis (p < or = .026). Mean left ventricular ejection fraction for the trastuzumab group was 57% before treatment and 56% after treatment. CONCLUSION: HER-2/neu is overexpressed in approximately one-third of esophageal adenocarcinomas. Trastuzumab can be added at full dose to cisplatin, paclitaxel, and radiation. Future studies of trastuzumab in esophageal adenocarcinoma are indicated.

Herceptin and gemcitabine for metastatic pancreatic cancers that overexpress HER-2/neu.

PURPOSE: To determine the response rate and toxicities of Herceptin and gemcitabine for patients with metastatic pancreatic adenocarcinomas that overexpress HER-2/neu. METHODS AND MATERIALS: Patients with metastatic pancreatic cancer with 2+/3 + HER-2/neu expression by immunohistochemistry were eligible. Patients received gemcitabine, 1 g/m2/week, for 7 of 8 weeks followed by 3 of every 4 weeks, and Herceptin, 4 mg/kg loading dose, followed by 2 mg/kg/week. RESULTS: Screening logs demonstrated the rate of HER-2/neu overexpression was 16%. Thirty-four patients were enrolled. Thirty patients (88%) had pancreatic cancers with 2+ overexpression and 4 patients (12%) had 3+ overexpression. Toxicity was similar to gemcitabine alone. Confirmed partial responses were observed in 2 of 32 patients (6%). Thirteen of 32 patients (41%) had either a partial response or a >50% reduction in CA 19-9. The median survival for all 34 patients was 7 months, and the 1-year survival was 19%. CONCLUSION: The response rate of Herceptin and gemcitabine is similar to gemcitabine alone. The 7-month median survival in patients with metastatic pancreatic cancer suggests there may be a modest benefit for some patients. Infrequent HER-2/neu overexpression limits the role of targeting the HER-2/neu gene and prevents definitive conclusions on the addition of Herceptin to gemcibine for patients with pancreatic cancer.