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Biomedical subjects

C Camps

Publications and source records attributed to C Camps.

At least 37 records · Page 2Linked to original sources

Preoperative high-dose cisplatin versus moderate-dose cisplatin combined with ifosfamide and mitomycin in stage IIIA (N2) non small-cell lung cancer: results of a randomized multicenter trial.

Preoperative chemotherapy has become an accepted treatment for stage IIIA (N2) non small-cell lung cancer (NSCLC). The majority of induction regimens employ cisplatin, although the importance of cis-platin dose in combination is unclear. A randomized trial was conducted to address whether higher pre-operative cisplatin doses result in improved survival and increased pathologic complete response in NSCLC. Patients with stage IIIA clinically enlarged and biopsy-proven N2 lesions were randomly assigned to receive either high-dose cisplatin (HDCP) (100 mg/m2) or moderate-dose cisplatin (MDCP) (50 mg/ m2) in combination with ifosfamide (3 g/m2) and mitomycin (6 mg/m2). Disease was restaged after 3 cycles, and those patients with response or stable disease underwent thoracotomy. From March 1993 to February 1997, 83 patients were randomized: 46 received HDCP, and 37 received MDCP. Clinical characteristics were well matched. Radiographic response rate was 59% for HDCP patients and 30% for MDCP patients (P = 0.01). Thoracotomy was performed in 71 patients (86%), 58 of whom had resectable disease. Complete resection rate was 61% in the HDCP group, and 51% in the MDCP group (P = 0.5). Postoperative mortality was 11%. Pathologic complete response was observed in one patient who received MDCP. Median survival in the HDCP and MDCP groups was 13 and 11 months, respectively (P = 0.3). In conclusion, higher radiographic response rate is observed in patients who receive HDCP, but this study fails to show any significant improvement in either overall survival or pathologic complete response in this group of patients.

Clinical Trial↗

Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: a 7-year assessment of a randomized controlled trial.

In 1989, we began a multicenter study to evaluate the potential benefit of preoperative chemotherapy with cisplatin, ifosfamide and mitomycin over surgery alone in CT-visible N2 non-small-cell lung cancer. We present here a 7-year assessment of this randomized trial. Sixty patients were randomized to receive either surgery alone or three cycles of mitomycin 6 mg/m2, ifosfamide 3 g/m2 and cisplatin 50 mg/m2, given intravenously on day 1 of each cycle at 3-week intervals and followed by surgery. All patients received thoracic irradiation after surgery. The resected tumors were evaluated for the presence of K-ras gene point mutations. Treatment arms were well-balanced in characteristics such as gender, age, histology, and tumor size. Mediastinoscopy and/or mediastinotomy (Chamberlain procedure) with a biopsy was performed in all patients with N2 stage detected by CT scan of the chest (83% of the patients in the preresectional chemotherapy arm and 63% of those in the surgery arm). In eight of the 25 patients (32%) who had mediastinoscopy in the preresectional chemotherapy arm, the initially positive mediastinal lymph nodes were downstaged. For the 30 patients who received preresectional chemotherapy, overall median survival was 22 months (95% CI, 13.4 30.6). Of the 30 patients who received surgery alone, overall median survival was 10 months (95% CI, 7.4-12.6; P = 0.005 by the log rank test). Updated survival data reveals a plateau in the preresectional chemotherapy group, and this still significant long-term survival benefit prompts us to hypothesize that even with short-term preresectional chemotherapy, the natural history of still resectable CT-visible N2 non-small cell lung cancer is favorably altered. The results of our study mirror the long-term survival recently reported in the MD Anderson randomized study.

Adult↗

Organochlorine in the serum of inhabitants living near an electrochemical factory.

OBJECTIVES: To measure the impact of occupational and lifestyle factors on concentrations of organochlorine compounds in a general population sample living near an electrochemical factory with a high airborne concentration of hexachlorobenzene (HCB). METHODS: Serum samples from 608 people (328 selected from a random sample) were collected in 1994. Information on lifestyles, occupation, and medical condition was obtained by questionnaire. RESULTS: HCB and polychlorinated biphenyls (PCBs) were detected in all samples (means 36.7 ng/ml and 4.3 ng/ml respectively), followed by dichlorodiphenyl dichloroethane (DDE) and beta-hexachlorocyclohexane (beta-HCH), found in 98.7% and 87.3% of the samples respectively (means 4.6 ng/ml and 2.5 ng/ml, respectively). Concentrations of HCB were the highest ever reported. Occupation in the factory was the main determinant of the variation in concentrations of HCB (regression coefficients 1.52 (SEM 0.14) in 1n (HCB) for workers in the production department, and 2.13 (0.23) for workers in maintenance department) and explained the highest concentrations of HCB found in men of middle age. In retired workers, concentrations of HCB declined with time since retirement. The PCBs, dichlorodiphenyl trichloroethane (DDT), and beta-HCH were independent of the occupation and concentrations were similar to those found in other populations. Concentrations of beta-HCH and DDE in the whole population, and HCB among non-workers, were higher in women than in men. Concentrations of all measured organochlorine compounds increased with age and body mass index. Consumption of locally caught fish was an independent determinant of HCB and PCB concentrations. CONCLUSIONS: This population incorporated HCB directly through occupation in the electrochemical factory, by airborne pollution, and consumption of locally caught fish. Concentrations of other common organochlorine compounds were not higher than expected. Environmental exposures to these compounds deserve attention due to their persistence and potential health effects.

Adolescent↗

Superiority of sequential versus concurrent administration of paclitaxel with etoposide in advanced non-small cell lung cancer: comparison of two Phase II trials.

Paclitaxel and etoposide are two chemotherapy agents with broad cytotoxic activity and different mechanisms of action and resistance. Preclinical studies of their combined cytotoxicity have yielded conflicting results. We performed two sequential Phase II trials using different sequence schedules of paclitaxel and etoposide as first-line treatment in advanced non-small cell lung cancer (NSCLC). Forty-four patients with stage IIIB or IV NSCLC were included between July 1995 and September 1996. All patients received etoposide at 100 mg/m2, given as an i.v. infusion on days 1, 2, and 3. The first 20 patients (part A) also received paclitaxel at 175 mg/m2 as a 3-h infusion on day 1, immediately prior to etoposide. The subsequent 24 patients (part B) were given the same paclitaxel dose, but on day 4. Grade 3-4 granulocytopenia was seen in 70% of the patients in part A and in 37% of those in part B (P = 0.04). Twenty-five % of the courses in part A and 4% of the courses in part B were associated with granulocyte nadir < or =500/microl (P = 0.00006). No responses were observed in part A, although disease was stabilized in 14 patients (70%). In part B, there were two complete responses and seven partial responses, for an overall response rate of 37.5% (95% confidence interval, 21-58%). In conclusion, toxicity and antitumor activity of the paclitaxel/etoposide combination may be sequence dependent. Our findings suggest that etoposide followed by paclitaxel is well tolerated and has greater activity in NSCLC than concurrent administration.

Adult↗

Modified weekly regimen with vinorelbine as a single agent in unresectable non-small cell lung cancer.

After a 26% response rate was reported with a 20/mg/m2/week vinorelbine (VRL) dose, a multicenter phase II trial of a modified weekly VRL treatment protocol (30 mg/m2 days 1 and 8 every 21 days) for unresectable non-small cell lung cancer (NSCLC) was designed to determine its clinical activity, toxicity, and survival of treated patients. As myelotoxicity frequently precludes the administration of VRL, by suppressing the dose that would correspond to day 15 of a weekly protocol, we allowed bone marrow recovery to take place and avoided the administration of the drug at the nadir of the cycle. The trial included 71 consecutive, previously untreated patients with unresectable and measurable disease. A total of 297 three-week treatment courses were administered with an average of 4 courses per patient (range 1-11). Results showed that in spite of attaining a median dose intensity of 19 mg/m2/week, this modified weekly VRL treatment regimen has a low level of activity (7.5% response rate) in NSCLC. Although a more tolerable level of toxicity is achieved, in order to maintain its antitumor activity, the recommended dose of VRL when given alone for NSCLC treatment (30 mg/m2/weekly) should not be decreased.

Adult↗

A sequence-dependent paclitaxel/etoposide phase II trial in patients with non-small cell lung cancer.

Studies conducted by the Spanish Lung Cancer Group indicate that cisplatin- or carboplatin-based chemotherapy can yield a 25% response rate, 9-month median survival time, and 30% 1-year survival rate in patients with stage III and IV non-small cell lung cancer. Phase II trials of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have an almost 30% response rate in non-small cell lung cancer. Based on these results, we decided to examine whether the sequence-dependent effects of paclitaxel/etoposide influence treatment outcome (antitumor response) and toxicity. In vitro data show a paradoxical antagonist rather than additive effect. In the first part of our study (part A), paclitaxel and etoposide were administered at the same time. In the second part (part B), etoposide preceded paclitaxel. In both parts, patients with previously untreated stage IIIB or IV non-small cell lung cancer with good performance status were eligible. In part A, etoposide (fixed dose, 100 mg/m2) on days 1, 2, and 3 was administered by 30-minute infusion; paclitaxel (175 mg/m2) was given by a 3-hour infusion on day 1. In part B, the etoposide dose and schedule were the same, but paclitaxel (same dose) was administered on day 4. Treatment in both parts was repeated every 21 days for a maximum of 10 cycles. In part A, 18 patients were entered and no objective responses were observed. In part B, 21 patients were accrued, 17 of whom had sufficient follow-up for response assessment. Seven objective responses were achieved (two complete and five partial responses, for an objective response rate of 41%). Seven patients had no change and three had progressive disease. Frequency and severity of side effects were not significantly different in either part of the study. However, grade 4 neutropenia was observed in 10 (59%) patients and one (5%) patient in parts A and B of the trial, respectively. Nonhematologic toxicity was slight. In conclusion, paclitaxel cytotoxicity is abrogated when it is given concurrently with etoposide. When etoposide precedes paclitaxel, a more effective paclitaxel/etoposide schedule is attained.

Adult↗

[An experimental short-term study of intramuscular integration of macroporous biphasic calcium phosphate ceramics. Application to the achievement of biocomposite flaps].

The aim of this research is to prefabricate a bicomposite flap, which can be defined as a composite structure of foreign material and living tissue. An animal model was developed by vascularizing spherical implants of macroporous biphasic calcium phosphate by a latissimus dorsi muscle flap in rabbits. The experiment was divided into three stages to compare the role of blood flow in the flap and autologous marrow bone cells. Biological apatite precipitation inside the macropores requires both factors and allows further clinical applications.

Animals↗

Mutated K-ras gene analysis in a randomized trial of preoperative chemotherapy plus surgery versus surgery in stage IIIA non-small cell lung cancer.

The observation that the proteins encoded by ras genes play a central role in the signalling pathways used by cells to respond to growth factors and the fact that mutated ras proteins are constantly promoting cell division have led to a PCR-based hunt for additional clinical information. In the present study, K-ras analysis draws the following conclusions: (1) K-ras point mutation frequency was higher in the surgery group (10 of 24 patients) than in the chemotherapy-surgery group (3 of 20 patients). (2) Mutated K-ras was predominantly observed at codon 12 but five mutations appeared at codon 61. (3) Mutations were identified in the squamous cell carcinoma histological NSCLC subtype except in four cases corresponding to adenocarcinoma. (4) A multifarious pattern of substitutions, especially at codon 12, were noted with aspartic K 12 substitutions more prone to develop bone metastases. (5) Although a genotypic K-ras classification of NSCLC may not yet be formulated, our accumulated data (unpublished) suggest a trend toward it. (6) Patients with mutated K-ras tumors in the surgery group had no different survival than those with normal K-ras. However our pooled data as well as other authors' results assert that mutated K-ras constitute an additional prognostic datum that deserves to be included together with TNM classification. In the design of new preoperative (neoadjuvant) chemotherapy trials, stratification of tumors by K-ras status deserves to be further investigated in order to correlate with response, relapse and survival. Mutated K-ras genotype merits further research. Finally, the paradigm of uneven histological distribution and mutated K-ras spectra among researchers should serve as a stimulus to search for further contributions in this field.

Antineoplastic Combined Chemotherapy Protocols↗

A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer.

BACKGROUND: The efficacy of surgery for patients with non-small-cell lung cancer is limited, although recent studies suggest that preoperative chemotherapy may improve survival. We conducted a randomized trial to examine the possible benefit of preoperative chemotherapy and surgery for the treatment of patients with non-small-cell lung cancer. METHODS: We studied 60 patients (59 men and 1 woman) with stage IIIA non-small-cell lung cancer. The patients were randomly assigned to receive either surgery alone or three courses of chemotherapy (6 mg of mitomycin per square meter of body-surface area, 3 g of ifosfamide per square meter, and 50 mg of cisplatin per square meter) given intravenously at three-week intervals and followed by surgery. All patients received mediastinal radiation after surgery. The resected tumors were evaluated by means of K-ras oncogene analysis and flow cytometry. RESULTS: The median period of survival was 26 months in the patients treated with chemotherapy plus surgery, as compared with 8 months in the patients treated with surgery alone (P < 0.001); the median period of disease-free survival was 20 months in the former group, as compared with 5 months in the latter (P < 0.001). The rate of recurrence was 56 percent in the group treated with chemotherapy plus surgery and 74 percent in the group treated with surgery alone. The prevalence of mutated K-ras oncogenes was 15 percent among the patients receiving preoperative chemotherapy and 42 percent among those treated with surgery alone (P = 0.05). Most of the patients treated with chemotherapy plus surgery had tumors that consisted of diploid cells, whereas the patients treated with surgery alone had tumors with aneuploid cells. CONCLUSIONS: Preoperative chemotherapy increases the median survival in patients with non-small-cell lung cancer.

Adult↗

A randomized trial of mitomycin/ifosfamide/cisplatin preoperative chemotherapy plus surgery versus surgery alone in stage IIIA non-small cell lung cancer.

The efficacy of surgery or radiotherapy as conventional treatment for stage IIIA non-small cell lung cancer (NSCLC) is limited. Recent studies have pointed out that preoperative chemotherapy may improve survival. To reconcile the two approaches, we undertook a multidisciplinary randomized trial to examine the possible synergism between preoperative chemotherapy and surgery in improved survival. Stage IIIA NSCLC patients were randomly assigned to receive either three preoperative courses of mitomycin/ifosfamide/cisplatin chemotherapy and surgery or surgery alone. The median survival was significantly greater in the chemotherapy plus surgery group than in the surgery group (26 months v 8 months; P < .001). However, the prognostic value of the mutated K-ras gene data presented awaits the analysis of larger sample populations. Similarly, the role of high-dose cisplatin in inducing higher pathologic complete remissions has to be corroborated in future randomized trials.

Antineoplastic Combined Chemotherapy Protocols↗

5-Fluorouracil, folinic acid, epidoxorubicin and cisplatin (FLEP) combination chemotherapy in advanced measurable gastric cancer. A phase II trial of the Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD).

BACKGROUND: Metastatic disease is a common problem in gastric cancer and the development of better chemotherapeutic regimens is a clear priority in gastrointestinal oncology. PATIENTS AND METHODS: Ninety consecutive, previously untreated patients with unresectable or measurable metastatic gastric cancer were included in a multicenter phase II trial with a combination of folinic acid (200 mg/m2) and 5-fluorouracil (400 mg/m2) days 1-3, with epidoxorubicin (60 mg/m2) and cisplatin (100 mg/m2) on day 2. RESULTS: A total of 376 courses of FLEP were given, with a median of four courses per patient. Objective responses were observed in 32 (35%) patients (CI at 95%: 25.7%-46.3%). Eight (9%) patients experienced clinical complete remissions. Median time to progression was 25 weeks for the entire group of patients and 38 weeks for responders. Myelosuppression was the primary toxicity. WHO grade 3 leukopenia appeared in 26 patients (29%). Ten presented episodes of febrile neutropenia requiring hospitalization, but no toxic deaths were observed. Grades 3 and 4 thrombocytopenia were seen in 8 and 1 patients, respectively. Median survival time was 8 months for all treated patients and 11 months for responders. CONCLUSIONS: The FLEP regimen is an active combination in advanced gastric cancer with moderate toxicity that warrants further testing in a phase III trial.

Adult↗

Etoposide (E) + epirubicin (E) + cisplatin (P) combination chemotherapy (EEP) in advanced gastric cancer: negative impact on clinical outcome. Spanish Cooperative Group for GI Tumor Therapy (T.T.D.).

One hundred nineteen patients with advanced gastric cancer were included in a study comparing EEP vs. FEM chemotherapy. The response rate was higher (30%) in patients on EEP than in those treated with FEM (p = 0.05). Severe leukopenia, anemia, alopecia and infection were significantly more frequent on EEP. In addition, because of its intrinsic toxicity, EEP chemotherapy has a negative impact on the performance status of patients treated with this regimen, more than half of whom presented at least one episode of severe symptomatic toxicity while on EEP chemotherapy. The median time to progression and median survival for EEP-FEM were 2.08-3.4 and 4.2-7.9 months, respectively. Our data do not support the use of EEP chemotherapy in patients with AGC.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of advanced colorectal cancer with recombinant interferon alpha and fluorouracil: activity in liver metastasis.

A cohort of 35 patients with advanced colorectal cancer, not previously exposed to chemotherapy, were included in a phase II study exploring the combination of interferon-alpha, 9 MU subcutaneously three times weekly, and 5-fluorouracil 750 mg/m2/day during 5 consecutive days in continuous intravenous infusion followed with weekly bolus injection of fluorouracil 750 mg/m2. Of 33 cases evaluable for activity; 5 patients achieved partial response and 3 complete response for an overall response rate of 24% (95%; confidence limit 11-42%). Most of the responses were observed in liver metastases, response rate = 30% (95%; CL 13-53%), with little activity observed in other sites; response rate 3% (95%; CL 8-16%), p = .0006. The median time to progression and median overall survival were 16+ (range 1+ to 48+) and 21+ weeks (range 1+ to 52+). All patients were evaluable for analysis of toxicity. Severe mucositis and diarrhea, present in 14 patients were the limiting side effects. Two patients developed progressive renal toxicity and died. Weakness, myalgia, and nonneutropenic fever were observed frequently, one patient developed dementia. This combination is able to induce major responses in patients with advanced colorectal cancer, particularly in liver metastasis. Additional trials evaluating this approach are indicated.

Aged↗

[Microangiopathic hemolytic anemia associated with mitomycin-C treatment].

We present a case of a patient with non-resected epidermoid carcinoma of the anal canal, treated with a combination of radiotherapy regional and chemotherapy according to MMC-Ufelos protocol. After the application of the fourth chemotherapy cycle, the patient presented microangiopathic hemolytic anemia associated to Mitomycin-C, which was treated with the application of recurrent plasmapheresis and restricted transfusions of red corpuscles concentrate. The physiopathology of this disorder and its therapeutical implications are review.

Acute Kidney Injury↗