Interleukin-17 may be a valuable serum tumor marker in patients with colorectal carcinoma.

The promotion of tumor growth is due to a combination of several mechanisms, including angiogenesis and the abundance of cell-derived inflammatory cytokines. The aim of this study was to investigate the serum levels of interleukin 17 (IL-17) and the expression of p53 and Vascular Endothelial Growth Factor (VEGF), in order to determine the relationship between these markers and serum IL-17 levels in patients with colorectal carcinoma. Serum levels of the proinflammatory cytokine IL-17 in patients with colorectal carcinoma (CRC) (n=40) and in a healthy group (n=37) were analysed by ELISA. Surgically resected specimens of 59 colorectal carcinomas were studied by immunohistochemical staining for VEGF and p53. Analyses by ELISA showed significantly higher IL-17 serum levels in patients with colorectal carcinoma than in control subjects (IL-17; mean 128.52+/-47.62 pg/ml vs. mean 101.91+/-22.46 pg/ml; p=0.022). We also found an inverse correlation between p53 expression and the level of IL-17 in the serum of patients with CRC. In fact, the serum concentration of IL-17 was significantly higher in patients who did not express p53 (p=0.023). There was no significant correlation between the expression of p53 and VEGF. However, concomitant expression of VEGF and p53 showed a significant correlation with the histological and nuclear grade of the carcinoma. The data presented in our study indicate that IL-17 might act as a valuable tumor marker in patients with CRC and that combined analysis of p53 and VEGF expression might provide additional information about tumor features.

Preliminary study of mononuclear phagocytosis during breast cancer therapy.

PURPOSE: To evaluate the eventual changes in the number and phagocytic functions of blood monocytes in breast cancer patients during surgical treatment and chemotherapy. MATERIALS AND METHODS: The absolute and relative number of peripheral blood leukocytes and monocyte phagocytic functions were determined at the time of diagnosis (I), following surgery (II), during (III) and after chemotherapy (IV) in 30 patients diagnosed with breast cancer. The control group consisted of 30 age-matched healthy women. RESULTS: The mean number of monocytes was significantly lower in cancer patients at diagnosis, while they increased following surgery reaching the control values. There were no postchemotherapy changes in the number of monocytes. Monocyte phagocytic activity was decreased at the time of diagnosis. Following surgery, the capacity of phagocytosis (CP) recovered to normal values, but the index of phagocytosis (IP) remained decreased. During and after chemotherapy, as well as one year after surgery, the IP still remained decreased. CONCLUSION: Our results showed that some properties of monocytes' phagocytic activity in cancer patients were decreased at diagnosis, returning back to normal range after surgical therapy. However, time is needed to confirm whether the alteration of IP may provide additional information when monitoring breast cancer patients.

Blood monocytes and tumor-associated macrophages in human cancer: differences in activation levels.

This study was performed to investigate functional properties of mononuclear phagocytes isolated from ascitic fluid in patients with peritoneal carcinomatosis (PC), and potential immunomodulatory effects of soluble factors produced or induced by human metastatic malignant cells. Phagocytic activity and nitric oxide production of peripheral blood monocytes (PBMo) and tumor-associated macrophages (TAM) or peritoneal macrophages (PEM) were synchronously examined in cancer patients and control individuals. Our results showed that contrary to peripheral blood monocytes, where phagocytic activity was not altered, TAM had impaired phagocytic activity. Moreover, dilutions of crude supernatant from short-term cultures of the peritoneal cells obtained from ascitic fluid of patient with PC, cause a significant, dose dependent inhibition of control PBMo and PEM phagocytosis, comparable to those in TAM, indicating that a soluble factor(s) plays a prominent role in this alteration. Next, we investigated the potential of cancer patients mononuclear phagocytes to produce nitric oxide (NO). It was found that TAM produce fourfold lower levels of NO than PEM from control subject, whereas monocytes produce NO at levels comparable to those of corresponding controls. These data support the hypothesis that depressed TAM function may contribute to the mechanisms of tumor escape from immune destruction.

Influence of interfraction interval on the efficacy and toxicity of hyperfractionated radiotherapy in combination with concurrent daily chemotherapy in stage III non-small-cell lung cancer.

PURPOSE: To investigate the influence of the interfraction interval (IFI) on treatment outcome and toxicity in hyperfractionated (HF) radiotherapy (RT) for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: Data for 301 patients treated with 1.2 Gy b.i.d. to a total of 69.6 Gy and concurrent chemotherapy in our 3 prospective studies were analyzed. The chemotherapy regimen was either (1) 50 mg each of carboplatin and etoposide (CE) given on RT days (163 patients) or (2) 30 mg of CE on RT days and 100 mg of CE on Saturdays and Sundays during the RT course (138 patients). An IFI of 4.5-5 h or 5.5-6 h had been nonrandomly assigned for each patient, and this interval was kept throughout the treatment. RESULTS: No difference was observed in treatment outcome due to the chemotherapy protocol, and the 2 groups were combined. Patients treated with the shorter IFI had a better local control rate (38% at 5 years) and survival rate (30% at 5 years) than those treated with the longer interval (23% and 14%, respectively; p < 0.001). However, female patients and those with a high Karnofsky performance status score (KPS), weight loss of < or =5% in the previous 6 months, or Stage IIIA disease had been more often treated with the shorter IFI, and these characteristics were associated with better treatment outcome. In multivariate analysis, only gender, KPS, and weight change proved to be significant prognostic factors influencing both local control and survival, and the effect of IFI was not significant. The incidence of Grade 4 acute esophagitis tended to be higher in the shorter interval group (p = 0.072), but there were no differences in the incidence of late or other acute RT-related toxicities between the 2 groups. CONCLUSIONS: The possible influence of the IFI on local control and survival could not be verified using multivariate analysis. To better understand the influence of the IFI, randomized studies with more patients and wider ranges of intervals (e.g., 5 h vs. 8 h) seem to be necessary.

Hyperfractionated radiation therapy and concurrent low-dose, daily carboplatin/etoposide with or without weekend carboplatin/etoposide chemotherapy in stage III non-small-cell lung cancer: a randomized trial.

PURPOSE: To investigate whether the addition of weekend chemotherapy consisting of carboplatin/etoposide to hyperfractionated radiation therapy (Hfx RT) and concurrent daily carboplatin/etoposide offers an advantage over the same Hfx RT/daily carboplatin/etoposide. METHODS AND MATERIALS: A total of 195 patients (Group I, 98; Group II, 97) were treated with either Hfx RT to a total tumor dose of 69.6 Gy via 1.2 Gy b.i.d. fractionation and daily 50 mg each of carboplatin and etoposide during the RT course (Group I) or the same Hfx RT with daily carboplatin/etoposide consisting of 30 mg each of carboplatin and etoposide and with weekend (Saturdays and Sundays) 100 mg each of carboplatin and etoposide during the RT course (Group II). RESULTS: No difference was found regarding median survival time and 5-year survival rates (20 vs. 22 months and 20% vs. 23%; p = 0.57). Median time to local progression was 20 and 19 months, respectively, while 5-year local progression-free survival rates were 28% and 27%, respectively (p = 0.66). Also, there was no difference regarding either median time to distant metastasis and 5-year distant metastasis-free survival (21 vs. 25 months and 29% vs. 34%, p = 0.29). There was no difference in the incidence of various nonhematologic toxicities between the two treatment groups, but patients treated with the weekend CHT had significantly more high-grade (> or = 3) hematologic toxicity (p = 0.0046). Late high-grade toxicity was not different between the two treatment groups. CONCLUSION: The addition of weekend carboplatin/etoposide did not improve results over those obtained with Hfx RT and concurrent low-dose, daily carboplatin/etoposide, but it led to a higher incidence of acute high-grade hematologic toxicity.

Second cancers occurring in patients with early stage non-small-cell lung cancer treated with chest radiation therapy alone.

PURPOSE: To investigate the incidence of second cancers occurring in patients with early stage (I/II) non-small-cell lung cancer (NSCLC) treated with radiation therapy (RT) alone. PATIENTS AND METHODS: Seventy-eight patients had been treated with conventionally fractionated (CF) RT (1982 to 1987), and 116 patients had been treated with hyperfractionated (Hfx) RT (1988 to 1993). Tumor doses were 60 Gy for CF and 69.6 Gy (1.2 Gy bid) for Hfx. RESULTS: A total of 26 patients developed second cancers. The cumulative incidence of second cancer was 21.8% (SE, 4.7%) at 5 years and 34.8% (SE, 6.7%) at 10 years. For second lung cancers, it was 6.0% (SE, 2.8%) at 5 years and 14.2% (SE, 5.2%) at 10 years, and for second nonlung cancers, it was 16.3% (SE, 4.2%) at 5 years and 22.2% (SE, 5.7%) at 10 years. The rate of developing second cancer per patient per year was 4.3% (95% confidence intervals [CI], 2.7% to 5.9%), with the rates being 1.4% (CI, 0.5% to 2.3%) for the second lung cancers and 2.8% (CI, 1.5% to 4.1%) for second nonlung cancers. The rate of developing second cancers during the first and second 5-year period after RT (0 to 5 and 5 to 10 years) was 4.3% (CI, 2.4% to 6.2%) and 4.2% (CI, 0.6% to 7.8%), respectively, for all cancers. These rates were 1.0% (CI, 0.1% to 1.9%) and 2.2% (CI, 0% to 4.6%), respectively, for second lung cancers, and 3.2% (CI, 1.6% to 4.8%) and 1.5% (CI, 0% to 3.6%), respectively, for second nonlung cancers. CONCLUSION: Long-term survivors after RT alone for early stage NSCLC carry the same risk of developing second cancer, either lung or nonlung, as their counterparts treated surgically when the results of this study are compared with those of the published literature.

Hyperfractionated radiotherapy for clinical stage II non-small cell lung cancer.

BACKGROUND AND PURPOSE: Patients with stage II non-small cell lung cancer who are not suitable for or refuse surgery are treated with radiotherapy, but the results reported so far are not satisfactory. To improve the prognosis of such patients, we have used hyperfractionated radiotherapy. In this paper, we retrospectively analyzed results of the treatment. MATERIALS AND METHODS: Between 1988 and 1993, 67 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 43 had medical problems and 24 refused surgery. The median age and Karnofsky performance status score was 60 and 90 years, respectively. No patient received chemotherapy or immunotherapy. The median follow-up period was 61 months. RESULTS: The median survival time and the 5-year survival rate were 27 months and 25% (standard error, SE, 6%), respectively. The 5-year local control rate was 44% (SE,7%). Univariate analysis of prognostic factors revealed that a higher Karnofsky performance status score, weight loss of < or =5% before treatment, and T1 stage were associated with better prognosis, and peripheral location was of borderline significance (P = 0.053). There were two bronchopulmonary and two esophageal acute grade 3 toxicities, and one bronchopulmonary and two esophageal late grade 3 toxicities. No grade 4 or 5 toxicity was observed. CONCLUSION: These results are encouraging and further studies on the use of hyperfractionation seem to be warranted for stage II non-small cell lung cancer.

A randomized trial of three single-dose radiation therapy regimens in the treatment of metastatic bone pain.

PURPOSE: To investigate efficacy of three single dose radiation therapy (RT) regimens in the treatment of painful bone metastasis. MATERIAL AND METHODS: Patient self-assessment by using pain chart enabled evaluation of response to treatment that consisted of either one of the three single fractions of 4 Gy (group I; n=109), 6 Gy (group II; n=108), or 8 Gy (group III; n=110). RESULTS: Patients in groups II and III had higher complete response rate than those in group I, but not significantly, and with no difference between group II and III. However, both patients in group II (73%) and group III (78%) had significantly higher overall response rates when compared to those observed in group I (59%) (I vs II, p=0.025; I vs III, p=0.0019), and with no difference between groups II and III (p=0.39). Patients in group III had shortest time to the occurrence of any pain relief which was significantly better than those observed in group I (Welch's t-test, p=0.012), with no difference between group I and II and group II and III, respectively. There was no difference between the three treatment groups in duration of response and retreatment rate. No effect of histology or metastatic site treated was found. No pathological fractures or spinal cord compressions were observed during the 8 weeks post-RT. CONCLUSION: Results of this study seem to confirm that 8 Gy could be considered as probably "lowest" optimal single fraction RT in the treatment of painful bone metastasis, although single fraction RT of 4 Gy should not be easily discarded due to its applicability in specific cases. Since single fraction RT of 6 Gy achieved results not different from that obtained with 8 Gy, further studies are warranted in order to get more informations about "lowest" optimal single fraction RT in the treatment of painful bone metastasis.

Accelerated hyperfractionated radiation therapy and concurrent 5-fluorouracil/cisplatin chemotherapy for locoregional squamous cell carcinoma of the thoracic esophagus: a phase II study.

PURPOSE: To improve the poor prognosis of patients with locoregional esophageal squamous cell cancer, we used concurrent accelerated hyperfractionated radiation therapy (ACC HFX RT) and chemotherapy (CHT). MATERIAL AND METHODS: Between January 1988 and June 1993, 28 patients were treated with ACC HFX RT with 1.5 Gy twice daily, to a total dose of 54 Gy concurrently with 5-fluorouracil (5-FU) (300 mg/m2, days 1-5) and cisplatin (CDDP) (10 mg/m2, days 1-5), both given during weeks 1 and 4 of the ACC HFX RT course. Following the ACC HFX RT/CHT, two additional courses of 5-FU (500 mg/m2, days 1-5) and CDDP (20 mg/m2, days 1-5) were both given during weeks 7 and 10. The median age and Eastern Cooperative Oncology Group performance status were 62 and 1, respectively. The American Joint Committee on Cancer (AJCC) stage was I in 12 patients, II in 10, and III in 6. RESULTS: The median survival time was 26 months, and the 5-year survival rate was 29%. The rates at 5 years for freedom from relapse, locoregional recurrence, and distant metastasis were 29%, 61%, and 45%, respectively. Univariate analysis revealed that performance status, stage, weight loss, tumor length, and tumor location influenced survival, while age and sex did not. The most frequent acute high-grade (3 or 4) toxicities were esophagitis and leukopenia, seen in 50% and 39% of patients, respectively. Late high-grade toxicity was infrequent. There were no treatment-related deaths. CONCLUSION: The results of this study compare favorably with those of previous studies, albeit of relatively high incidence of acute high-grade toxicity. Further studies are warranted to compare its efficacy with other approaches.

Carboplatin, etoposide, and accelerated hyperfractionated radiotherapy for elderly patients with limited small cell lung carcinoma: a phase II study.

BACKGROUND: It is not clear how well elderly patients with limited small cell lung carcinoma tolerate intensive chemotherapy, and they have often been treated with palliative intent. As an alternative strategy, the authors designed and employed a short term combination regimen consisting of carboplatin and etoposide with accelerated hyperfractionated radiotherapy. METHODS: Seventy-five patients ages > or = 70 years with a Karnofsky performance status of > or = 60 and no other major medical problems, were enrolled in this study and 72 were evaluable. The protocol consisted of intravenous carboplatin (400 mg/m2) given on Days 1 and 29, oral etoposide (50 mg/m2) given on Days 1-21 and 29-49, and accelerated hyperfractionated radiation at a dose of 1.5 gray (Gy) administered twice daily (total dose, 45 Gy) starting on Day 1. RESULTS: The median follow-up period was 61 months. The response rate was 75%, and complete response was observed in 57% of the patients. The median survival time was 15 months, and the 2- and 5-year survival rates were 32% and 13%, respectively. Acute Grade 3 leukopenia, thrombocytopenia, and esophagitis were observed in 8.3%, 11%, and 2.8% of the patients, respectively. Only one patient experienced Grade 4 acute toxicity (thrombocytopenia). No late toxicity of Grade 3 or higher was observed. CONCLUSIONS: This combined treatment program was tolerable and produced promising long term results. Elderly patients should not universally be treated with palliative intent. Further studies exploring a potentially more effective regimen are warranted.

Absence of thoracic radiation myelitis after hyperfractionated radiation therapy with and without concurrent chemotherapy for Stage III nonsmall-cell lung cancer.

PURPOSE: To investigate whether thoracic spinal cord dose of 50.4 Gy given via 1.2 Gy b.i.d. fractionation carries a risk of developing radiation myelitis during studies using hyperfractionated radiation therapy (HFX RT) with and without concurrent chemotherapy (CHT). METHODS AND MATERIALS: Of 300 patients with Stage III nonsmall-cell lung cancer (NSCLC) who were treated on two consecutive Phase III studies, 158 patients received 50.4 Gy to a portion of their spinal cord and survived > 1 year after the beginning of the therapy. RESULTS: None of these 158 patients developed thoracic radiation myelitis. Therefore, influence of potentially contributing factors on the occurrence of radiation myelitis, such as interfraction interval, or those unproven yet, such as cord length or administration of concurrent CHT, was not possible to investigate. CONCLUSION: Given the continuing interest in HFX RT and encouraging results obtained in studies in lung cancer, further investigation is needed to get more informations about risks of developing thoracic radiation myelitis with this cord dose.

Prolonged administration of oral etoposide alone or with intravenous carboplatin in stage IV non-small cell lung cancer: a randomized trial.

BACKGROUND: To investigate whether the addition of intravenous carboplatin (CBDCA) to prolonged oral administration of etoposide improves treatment results over that obtained with the same etoposide given alone in patients with Stage IV non small-cell lung cancer (NSCLC). MATERIAL AND METHODS: Patients, 120 were randomized to receive either 400 mg/m2 of CBDCA, day 1 and 50 mg/m2 of etoposide, days 1-21 (Group I) or the same etoposide alone (Group II). Cycles were repeated every 4 weeks for up to 6 cycles or until tumor progression was noted. RESULTS: Patients, 117 were fully evaluable for this report. Patients in Group I achieved better response rate than those in Group II (31 versus 20%, P = 0.19). They also had longer median survival time and higher 1- and 2-year survival rates than those in Group II (9 versus 5 months, respectively; 38 and 12% versus 24 and 5%, respectively; P = 0.015). There were no treatment-related deaths. Leukopenia (P = 0.047) and thrombocytopenia (P = 0.000) were more frequent in Group I, but only 15 (26%) patients in Group and 7 (12%) patients in Group II experienced high-grade (> or = 3) hematological toxicity. Apart from alopecia (P = 0.000), other non-hematological toxicity was not different between the two treatment Groups. CONCLUSION: Results of this study showed improvement in survival for the two-drug regimen. Together with mild to moderate toxicity and low cost, they may warrant further studies comparing it with other approaches in patients with Stage IV NSCLC.

Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer.

PURPOSE: Among patients with Stage I nonsmall cell lung cancer (NSCLC), those treated with conventional radiotherapy show poorer prognosis than those treated by surgery. To improve the prognosis of such patients, we have used hyperfractionated radiation therapy. METHODS AND MATERIALS: Between 1988 and 1993, 49 patients were treated with hyperfractionated radiotherapy with 1.2 Gy twice daily to a total dose of 69.6 Gy. All patients were technically operable, but 29 had medical problems and 20 refused surgery. The median age and Karnofsky Performance Status was 63 years and 90, respectively. No patient received chemotherapy or immunotherapy. Prophylactic mediastinal irradiation was not given. RESULTS: The median survival time was 33 months, and the 5-year survival rate was 30%. The rate at 5 years for freedom from each of relapse, local recurrence, mediastinal lymphnode metastasis, and distant metastasis was 41%, 55%, 89%, and 75%, respectively. Univariate analysis revealed that higher Karnofsky Performance Status score, absence of weight loss before treatment, and T1 stage were associated with better survival, although the T stage became insignificant on multivariate analysis. There were two Grade 3 acute toxicities and three Grade 3 late toxicities, but there was no Grade 4-5 toxicity. CONCLUSION: The results of this study compare favorably with those of most previous studies employing conventional fractionation. Further studies on hyperfractionation seem to be warranted for Stage I NSCLC.

Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study.

PURPOSE: To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS: Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17. RESULTS: The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity. CONCLUSION: Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration.

Radiotherapy for primary squamous cell carcinoma of the trachea.

Twenty-two patients with tracheal squamous cell carcinoma were treated by radiotherapy alone. Nine patients were treated with 60 Gy between 1982 and 1987 and 13 with 70 Gy between 1988 and 1993 using conventional fractionation. The median survival was 24 months and the 5-year survival rate was 27%. Patients receiving 70 Gy had a slightly better prognosis than those receiving 60 Gy, but the difference was not significant. Patients with mediastinal lymph node involvement had a significantly worse prognosis. Delayed tracheal toxicity tended to be higher in the 70 Gy group.

Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study.

PURPOSE: To investigate the efficacy of concurrent hyperfractionated radiation therapy (HFX RT) and low-dose daily chemotherapy (CHT) in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between January 1990 and December 1991, 131 patients with histologically or cytologically confirmed stage III NSCLC, Karnofsky performance status (KPS) > or = 50, and no previous therapy were randomly treated as follows: group I, HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy (n = 66); and group II, same HFX RT with CHT consisting of 50 mg of carboplatin (CBDCA) and 50 mg of etoposide (VP-16) given on each RT day (n = 65). RESULTS: Group II patients had a significantly longer survival time than group I patients, with a median survival of 22 versus 14 months and 4-year survival rates of 23% versus 9% (P = .021). The median time to local recurrence and 4-year local recurrence-free survival rate were also significantly higher in group II than in group I (25 v 20 months and 42% v 19% respectively, P = .015). In contrast, the distant metastasis-free survival rate did not significantly differ in the two groups (P = .33). The two groups showed similar incidence of acute and late high-grade toxicity (P = .44 and .75, respectively). No treatment-related toxicity was observed. CONCLUSION: The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control.

Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer.

PURPOSE: To investigate the efficacy of combined hyperfractionated radiation therapy (HFX RT) and concurrent chemotherapy (CHT) in stage IIIA or IIIB non-small-cell lung cancer (NSCLC) compared with that of HFX RT alone. PATIENTS AND METHODS: Between January 1988 and December 1989, 169 patients were divided randomly into the following groups: group I, HFX RT with 1.2 Gy twice daily to a total dose of 64.8 Gy (n = 61); group II, same HFX RT with CHT consisting of 100 mg of carboplatin (CBDCA) on days 1 and 2 and 100 mg of etoposide (VP-16) on days 1 to 3 of each week during the RT course (n = 52); and group III, same HFX RT with CHT consisting of 200 mg of CBDCA on days 1 and 2 and 100 mg of VP-16 on days 1 to 5 of the first, third, and fifth weeks of the RT course (n = 56). RESULTS: The median survival time (MST) was 8 months for group I, 18 months for group II, and 13 months for group III. The 3-year survival rates were 6.6%, 23%, and 16%, respectively. There was a significant difference in the survival rate between groups I and II (P = .0027, log-rank test), but not between groups I and III (P = .17) or between groups II and III (P = .14). The relapse-free survival rate in group II was also higher than that in group I (P = .0024), which was largely due to improved local control in group II patients. Patients in groups II and III showed a higher incidence of acute and/or late high-grade toxicity compared with group I patients, but no patient died of treatment-related toxicity. CONCLUSION: The combination of HFX RT and continuous CBDCA/VP-16 CHT was tolerable and substantially increased the survival rate.

Carboplatin and etoposide in patients with advanced gastric cancer.

Thirty-six patients with advanced gastric cancer were treated with combination chemotherapy following surgery. Chemotherapy consisted of carboplatin (CBDCA) 300 mg/m2, days 1-3, and etoposide (VP 16) 100 mg/m2, days 1-5. 10/36 (28%) patients had objective response. The median duration of response was 8 months. Currently 26/36 patients have shown progressive disease at a median of 4 months. Three patients remain progression-free 7, 14, and 15 months after study entry, respectively. 26/36 patients have died and 10/26 remain alive at a median time of 16 months. Estimated survival for all patients is 7 months. Two groups of toxicities were observed: hematological and gastrointestinal. They were generally assessed as mild with only two grade 3 (ECOG) toxicities and with no grade 4 toxicity observed during this study.

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.