Radioiodine therapy accelerates apoptosis in peripheral blood lymphocytes of patients with differentiated thyroid cancer.

Both apoptosis and micronuclei formation reflect cytogenetic damage in cells and could contribute to cell homeostasis. The aim of this study was to evaluate apoptosis in peripheral blood lymphocytes (PBLs) of patients with differentiated thyroid cancer (DTC) before and after 131-iodine (131-I)-therapy and its correlation with micronuclei (MN) frequency. The study population included 18 DTC patients and 18 healthy donors. Apoptotic cells were detected using the Annexin V-FITC/7-AAD kit and MN frequency by cytokinesis-block MN assay. The difference between early apoptosis in PBLs of DTC patients before therapy and controls (9.88 ± 4.99% vs. 6.64 ± 2.07%, p = 0.003) was significant, as well as between early apoptosis in PBLs of DTC patients before and after 131-I-therapy (9.88 ± 4.99% vs. 13.53 ± 6.57%, p = 0.008). The MN frequency and early apoptosis in PBLs of DTC patients was positively correlated before (r = 0.540, p= 0.021) and after 131-I-therapy (r = 0.585, p= 0.014). Thyroid cancer patients had a significantly increased early apoptosis in PBLs, which further increased after 131-I-therapy in association with MN frequency.

Hyperfractionated radiation therapy with and without concurrent chemotherapy for advanced non-small cell lung cancer.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) continues to be a frustrating challenge for oncologists. In this group of patients, the overall 5-year survival rates have been 3-6% in prospective randomized trials with radiation therapy (RT) alone. METHODS: One hundred sixty-nine patients, 18 years of age or older, with histologically or cytologically proven, advanced, nonresectable NSCLC; a Karnofsky performance status score of 50 or greater; and no previous therapy were treated as follows: treatment arm 1: hyperfractionated radiation therapy (HFX RT) to a total tumor dose of 64.80 Gy (61 patients); treatment arm 2: HFX RT to the same tumor dose with chemotherapy (CT) consisting of 100 mg of carboplatin, days 1 and 2, and 100 mg of etoposide (VP-16), days 1-3, given every week during the RT course (52 patients); and treatment arm 3: HFX RT to the same tumor dose with CT consisting of 200 mg of CBCDA, days 1 and 2, and 100 mg of VP-16, days 1-5, during the first, third, and fifth weeks of the RT course (56 patients). Acute and late toxic effects were scored from 0 (none) to 5 (fatal), according to the Radiation Therapy Oncology Group classification. RESULTS: The authors observed acute overall Grade 3 toxic effects in 11.5% of patients in treatment arm 1, 13.4% of patients in treatment arm 2, and 16.1% of patients in treatment arm 3. Acute overall Grade 4 toxic effects were observed in 1.6% of patients in treatment arm 1, 3.8% of patients in treatment arm 2, and 10.7% of patients in treatment arm 3. Regarding late toxic effects, we observed late overall Grade 3 toxic effects in 3.3% of patients in treatment arm 1, 11.6% of patients in treatment arm 2, and 15.4% of patients in treatment arm 3. Late overall Grade 4 toxic effects were observed in treatment arms 2 and 3 only: 3.8% in treatment arm 2 and 8.9% in treatment arm 3. No Grade 5 toxic effects were observed during this study. CONCLUSIONS: The acute toxic effects observed during this study in treatment arms 1 and 2 are at least comparable to those previously published in other studies of this type, but a high incidence of acute overall toxic effects was observed in treatment arm 3. Regarding late toxic effects, the authors observed a higher incidence of Grade 3 overall late toxic effects in treatment arm 2 and a high incidence of Grade 4 overall late toxic effects in treatment arm 3. Results of this study show that the addition of CT to HFX RT carries a risk of increased high-grade toxic effects, both acute and late.

Carboplatin and etoposide in advanced colorectal carcinoma. A phase II study.

BACKGROUND: For advanced colorectal carcinoma, 5-fluorouracil (5-FU)-leucovorin is the best therapy available. To improve results, a variety of drugs were added, including cisplatin (CDDP), sometimes with controversial results. The combination of CDDP and etoposide (VP-16) has shown synergistic activity in other settings. Although VP-16 alone is considered rather inactive in colorectal carcinoma, the authors believed it was appropriate to evaluate the combination of VP-16 and carboplatin (CBDCA) in this disease because the newer platinum analogue CBDCA has more limited side effects than the parent compound. METHODS: Twenty-eight patients with advanced colorectal carcinoma were treated with CBDCA (200 mg/m2, days 1-3) and VP-16 (100 mg/m2, days 1-5). Cycles were repeated every 4 weeks. All patients received at least two cycles (median, six cycles; range, two to eight cycles). RESULTS: There were three complete responses and four partial responses. The median duration of response was 35 weeks (range, 25-84 weeks). The median time to tumor progression was 23 weeks (range, 9-84 weeks). The median survival time was 49 weeks (range, 9-151+ weeks). Toxic effects generally were assessed as mild, with no Grade 4 (Eastern Cooperative Oncology Group classification) toxic effects observed during this study. CONCLUSIONS: Response rate and toxic effects observed during this study warrant additional studies comparing this regimen with 5-FU-based regimens in advanced colorectal carcinoma.

[Quantitative analysis of gallbladder function using quantitative dynamic radionuclide cholecystography]. / Kvantitativna analiza funkcije holeciste metodom kvantitativne dinamicke radionuklidne holecistografije.

The aim of the study is to demonstrate general function of the cholecyst through selected quantitative parameters derived from the quantitative radionuclide cholecystography method, using our own computer software HIDATA, and to evaluate values of specific quantitative parameters in 15 patients presenting with chronic calculous and 15 with chronic acalculous cholecystitis. A control group comprised 10 subjects with no changes on the cholecyst. Of four quantitative parameters calculated during cholecyst filling, the only significant one was the ascending segment slope of the curve from specific ROI, that is, K1 derived from it, because it shows its functional status, depending on the changes in its wall and the lumen content. The most significant parameters which maintain motor function of the cholecyst are ejection fraction (EF) and ejection rate (ER) which are always decreased in chronic cholecystitis, regardless of the presence of calculosis and the number of calculi in the lumen. The ejection fraction is especially decreased in the multiple sclerosis group; it is significantly decreased when compared with acalculous chronic cholecystitis. Our results indicate that a selection of parameters used in clinical practice for the assessment of the cholecyst function is necessary. Our program HIDATA included a large number of parameters of which three were classified as important for the assessment of the cholecyst function (K1, EF, ER), reflecting the process of filling and emptying of the cholecyst and offering reliable and valuable data for the treatment.

Carboplatin and etoposide chemotherapy regimen for recurrent malignant glioma: a phase II study.

PURPOSE: A phase II study that used combination chemotherapy with carboplatin (CBDCA) and etoposide (VP 16) (CE) was performed on patients with recurrent malignant glioma to investigate tumor control and toxicity. PATIENTS AND METHODS: Thirty-eight patients were treated with CBDCA 300 mg/m2 on days 1 to 3 and VP 16 100 mg/m2 on days 1 to 5. A minimum of three courses were required unless the patient had a rapid progression of disease (PD). Courses were repeated every 4 weeks. RESULTS: We observed partial responses (PRs) in eight of 38 patients (21%), stable disease (SD) in 12 of 38 (32%), whereas 18 of 38 (47%) patients had PD. The median time to tumor progression (TTP) for PR and SD patients was 42.5 weeks, whereas the median survival time (MST) for PR and SD patients was 47.5 weeks. Three groups of toxicities were observed: hematologic, gastrointestinal, and hepatic. No grade 4 Eastern Cooperative Oncology Group toxicity was observed. CONCLUSIONS: This regimen has shown at least comparable results with other series that used platinum-based agents. Further studies that use these agents in various-dose schedules and drug combinations are warranted.

Carboplatin and radiation therapy for stage IV carcinoma of the head and neck. Preliminary results of a phase II study.

34 patients with head and neck cancer were treated with carboplatin and radiation therapy. Eligibility criteria included stage IV biopsy-proven squamous cell carcinoma with measurable disease and no distant metastases, Karnofsky performance status score of 60 or greater, age 18 years or more, no previous radiation therapy and adequate hematological, renal, and hepatic function. There were 27 males and 7 females. Ages ranged from 44-70 years with a median of 57 years. Follow-up ranged from 11-34 months with a median of 21 months. Total tumor doses ranged from 50-55 Gy with additional boosts of 15-20 Gy. Carboplatin was given in a dose of 100 mg/m2 once weekly (26 patients) and 200 mg/m2 once every 2 weeks (8 patients), during the radiation therapy course in all 34 patients. Each dose of carboplatin preceded irradiation. 25 patients responded while 9 did not. There were 19 complete responses (CR) and 6 partial responses. 4/19 CR recurred and 5/9 non-responding patients died of disease. Mild to moderate nausea and vomiting were seen in 52.3% of patients and mucositis was seen in 61.8% of patients. Moderate to severe hematological toxicity was seen in 35.3% of patients. Response rates and toxicity we observed during this study clearly show that the combination of carboplatin and radiation therapy is effective and suitable for the treatment of patients with stage IV head and neck cancer.

Advantage of post-radiotherapy chemotherapy with CCNU, procarbazine, and vincristine (mPCV) over chemotherapy with VM-26 and CCNU for malignant gliomas.

Between 1981 and 1987, 133 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with surgery and post-operative radiotherapy. 36 AA and 31 GBM patients were treated with adjuvant chemotherapy consisting of CCNU 100 mg/m2 day 1, procarbazine 60 mg/m2 days 1-14, and vincristine 1.4 mg/m2 (max. 2 mg) days 1 and 8, every 6 weeks which we called a "modified PCV" (mPCV) regimen. 37 AA and 29 GBM patients were treated with adjuvant chemotherapy consisting of VM-26 75 mg/m2 days 1 and 2, and CCNU 60 mg/m2 days 3 and 4, every 6 weeks. Prognostic covariates such as patient's age, Karnofsky performance status score and the extent of surgery were balanced between the two treatment groups. The time to tumor progression and survival time for both regimens show that mPCV produces a two-fold increase in these factors at the 50th and 25th percentile for AA patients, but not for GBM patients, although there are more long-term GBM survivors with mPCV than with the VM-26 + CCNU regimen.

Metastatic squamous cell carcinoma of an unknown primary tumor localized to the neck.

68 patients with metastatic squamous-cell carcinoma (SCC) of an unknown primary tumor localized to the neck were treated between 1981 and 1990. There were 11 patients treated with radiotherapy alone, 24 patients treated with surgery and radiotherapy and 33 patients treated with radiotherapy and chemotherapy. Male to female ratio was 1.9:1 and the median age was 55 years (range, 33 to 71 years). 41 (61%) patients had N3 disease, 18 (26%) patients had N2 disease and 9 (13%) patients had N1 disease. The majority of N3 patients were treated with radiotherapy + chemotherapy (n = 17) and surgery + radiotherapy (n = 17). The complete response (CR) to radiotherapy + chemotherapy was 73% with 19 patients having no evidence of disease currently. The median survival time (MST of this group was 34+ months. Of the 35 patients who had surgery and/or radiotherapy, 7 (20%) currently have no evident disease. The MST of these two groups (combined) was 22 months. Patients with N3 disease who received radiotherapy + chemotherapy had a higher CR rate and longer MST when compared with those without chemotherapy.

Incidence of radiation myelitis of the cervical spinal cord at doses of 5500 cGy or greater.

The incidence of permanent damage to the spinal cord as a complication of radiation therapy generally correlates positively with total radiation dose. However, several reports have indicated that fraction size is also an important factor in the development of late damage in normal tissue. To determine the effect of fraction size on the incidence of radiation-induced spinal cord damage, the authors reviewed 176 cases of head and neck cancer treated at their department between 1980 and 1990 with radiation doses of 5500 cGy or greater to a portion of the cervical spinal cord. Majority of these patients received 6000 cGy or greater with fraction size ranging from 150 to 200 cGy. Seventy-two of 176 patients have been observed for 2 years or more. More than one third (26 patients) of these received greater than 6000 cGy with fraction sizes of 157 to 170 cGy. Four of 72 (5.6%) patients had experienced permanent cervical spinal cord damage. The results of this study suggest that radiation damage to the cervical spinal cord correlates not only with total radiation dose, but also with fraction size. Low fraction sizes appear to decrease the incidence of such damage.

Carboplatinum and cytosine arabinoside in patients with disseminated malignant melanoma. A phase II study.

Eighteen patients with disseminated malignant melanoma were treated with a combination of carboplatinum and cytosine arabinoside. There were 14 males and 4 females with median age of 51 years (range 36-68 years). We observed 4 complete responses (CR) and 3 partial responses (PR). Lung metastases, cutaneous and subcutaneous metastases responded more often, while liver and lymph node metastases did not respond. Two groups of toxicities were observed: gastrointestinal and hematological. Only nine grade 3 toxicities were observed. Response rates and low toxicity we observed during this study warrant its use for patients with disseminated malignant melanoma comparing it in a future studies with DTIC containing regimens.

Severe late intestinal complications after abdominal and/or pelvic external irradiation with high energy photon beams.

A total of 264 patients were treated between January 1981 and December 1985 for abdominal and/or pelvic tumours with high energy photon beams. Pelvic irradiation encompassed the true pelvis with upper limit located at the L5-S1 junction for 126 patients, at the L4-L5 junction for 107 patients with only 31 patients receiving external irradiation with treatment fields extending up to T12. The dose delivered to the pelvis was in the range 40-50 Gy with 72 (27.27%) patients receiving an extra dose on limited volumes up to 60-65 Gy. Acute intestinal reactions were observed in 38 (14%) patients. Using the Chassagne grading, we observed 14 grade 1,9 grade 2,13 grade 3 and 2 grade 4 late intestinal complications. Incidence of severe late intestinal complications in our series was 5.67% (15/264). Among these 15 patients three died of progression of the disease outside the treated volume, two died because of intestinal complications and/or their treatment and two died of unknown reasons. The remaining eight patients are alive with no evidence of the disease but with marked impairment of their intestinal functions. The analysis of risk factors showed only previous surgery (with laparotomy) to be significant, whereas age, delivered dose and treatment field and marked obesity had no influence on incidence of severe late intestinal complications.

Cardiotoxicity during chemotherapy treatment with 5-fluorouracil and cisplatin.

Cardiotoxicity of 5-fluorouracil and cisplatin chemotherapy for esophageal, head and neck and gastric carcinoma was studied. Before treatment all patients had a cardiac evaluation and during treatment serial electrocardiographic (ECG) recordings were performed. In the pre-treatment evaluation signs of cardiovascular disease were found in 31(38.75%) patients. During treatment cardiotoxicity was observed in 12(15%) patients. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and arrhythmia. This study suggests that patients on 5-fluorouracil and cisplatin treatment should be under close supervision and that the treatment should be discontinued if chest pain and/or arrhythmias are observed.

Acute toxicity from BOPP (BCNU, vincristine, procarbazine, cisplatinum) chemotherapy for glioblastoma multiforme.

Between January 1988 and October 1988, we treated 12 patients with glioblastoma multiforme with BOPP chemotherapy after surgery and radiotherapy. The protocol consisted of BCNU 50 mg/m2 days 1-3, vincristine 1.4 mg/m2 (maximum 2 mg) day 1, procarbazine 50 mg/m2, days 1-7 and cisplatinum 20 mg/m2, days 1-3. All patients had at least three courses of chemotherapy ECOG toxicity criteria were used. We observed 9/12 changes in WBC, 7/12 in Hgb. All patients had nausea and vomiting. We also observed 2/12 neuropathies related to CNS. Other toxicities were not observed.