Current Chemoradiotherapy Research Articles

Concurrent chemoradiotherapy for squamous cell carcinoma of the anus using a shrinking field radiotherapy technique without a boost.

Chemoradiotherapy (CRT) is now widely accepted as the primary treatment modality for squamous cell cancer of the anus. While randomised trials have clearly shown CRT to be more effective than radiotherapy alone, there remains uncertainty over the optimal integration of chemotherapy and radiation. We describe a series of 50 patients treated by a site specialist gastrointestinal nonsurgical oncologist with CRT at a single UK centre. Chemotherapy comprised mitomycin C (MMC) (day 1) and 5-fluorouracil (5-FU) (days 1–4, and 29–32), concurrent with 50 Gy in 25 fractions radiation, using a two-phase shrinking field technique. A radiation boost was not planned. At a median follow-up of 48 months, 11 (22%) of the patients have failed locally, of which three have been surgically salvaged. Nine (18%) have died of anal cancer. These results are comparable with those from large randomised studies, and suggest that a two-phase shrinking field radiotherapy technique with no boost, concurrent with MMC/5-FU chemotherapy, is an effective regimen for this disease. The CRT regimen described here provides the basis for the ‘control arm’ of the current UK-randomised CRT trial in anal cancer (ACT2).

A novel approach for examining the anti-proliferative effect of protein kinase C inhibitors against human astrocytoma cells.

Prognosis for astroglial brain tumors that are not amenable to surgical resection remains poor and even successful treatment with current chemoradiotherapy is associated with debilitating sequelae. Consequently, a need to identify novel therapeutics for the treatment of brain tumors remains. Regulation of protein kinase C (PKC) whose activity regulates many cellular functions is crucial for maintaining normal cellular proliferation. Recent reports indicate that malignant glioma cell lines express 100 to 1000-fold higher PKC activity when compared to non-neoplastic astrocytes. In this study we used a novel approach for the evaluation of known PKC inhibitors (CGP 41251, Go 6976, and tamoxifen) as chemotherapeutic agents for the inhibition of growth of an astroglial derived cell line. For this purpose, we constructed a model cell system based on the measurement of light production in cells transfected with the luciferase reporter gene whose expression was quantitated by a highly sensitive, rapid, and easy to perform assay. We isolated U-373MG/MEK1C clone whose highly increased luciferase activity was independent of external stimuli and directly proportional to cell number, and therefore, was used as a measure of cell proliferation to quantitate the effects of several PKC inhibitors on growth of astrocytoma cells in vitro. In conclusion, we have constructed a novel cell system that can be utilized for high throughput screening and identification of potential anti-cancer drugs active against astrocytoma cells in culture.

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.