Weekly administration of topotecan-paclitaxel as second-line treatment in ovarian cancer.

PURPOSE: To investigate the weekly administration of topotecan combined with paclitaxel in pretreated advanced ovarian cancer patients; our objectives were to determine efficacy, toxicity and survival. METHODS: The chemotherapy agents, topotecan and paclitaxel were administered on a weekly basis for 3 consecutive weeks, every 28 days. The plan was to give three courses (each course included three once-weekly infusions). The dose of topotecan was 1.75 mg/m(2) and of paclitaxel 70 mg/m(2). RESULTS: From January 2004 until January 2006, 45 patients were enrolled in this multicenter trial; 44 patients were evaluable for response and toxicity. The median age was 60 years old (range 39-82 years) and performance status was 0-2. Thirty-nine patients were in stage III and 5 in stage IV. All patients had been pretreated with carboplatin or cisplatin in combination with paclitaxel. Complete and partial responses were seen in 39% of the patients, stable disease in 43% and progressive disease in 18%; median survival time was 9 months, range 2-24+ months, (95% CI: 7.9-10.2). There was a notable absence of grade 3 toxicity except for neutropenia in 11% of the patients. CONCLUSION: The combination of topotecan and paclitaxel administered on a weekly basis is a well-tolerated chemotherapy schedule. The response rate of 39% is quite high for patients with pretreated ovarian cancer.

Phase II study of paclitaxel, ifosfamide, and cisplatin as second-line treatment in relapsed small-cell lung cancer.

PURPOSE: The aim of the present phase II study was to evaluate the efficacy of the paclitaxel, ifosfamide, and cisplatin (PIC) combination in relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were those with SCLC who had progressed or relapsed after therapy with carboplatin and etoposide (with or without chest radiotherapy). The PIC regimen consisted of paclitaxel 175 mg/m(2) on day 1, ifosfamide 5 g/m(2) divided over days 1 and 2, and cisplatin 100 mg/m(2) divided over days 1 and 2; PIC was given every 21 days with granulocyte colony-stimulating factor support. RESULTS: Thirty-three patients (30 men and three women) were entered onto the study (median age, 62 years [range, 55 to 70 years]; median performance status, 1 [range, 0 to 2]). Metastatic sites at study entry included the lymph nodes (n = 13 patients), bone (n = 9), liver (n = 5), brain (n = 6), lung nodules (n = 8), adrenal glands (n = 9), and other (n = 2) Responses included eight complete remissions and 16 partial remissions (overall response rate, 73% [24 of 33 patients]). Five patients had stable disease and two had progressive disease. Median time to progression and overall survival were 21 and 28 weeks, respectively. The 1-year survival rate was 12%, with two patients alive without evidence of disease at 76 and 104 weeks since PIC initiation. Grade 3 and 4 toxicities included neutropenia in 30 patients (24 [73%] developed grade 4 neutropenia [ < 5 days]) and febrile neutropenia in six patients (18%); grade 3 or 4 thrombocytopenia was seen in nine patients (27%). No grade 3 neuropathy was observed; grade 1 or 2 CNS toxicity was seen in five patients, there was no renal toxicity, grade 2 myalgias were seen in nine patients, grade 2 diarrhea was seen in one patient, and grade 3 nausea or vomiting was seen in seven patients. There were no treatment-related deaths. CONCLUSION: In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned.

Irinotecan combined with docetaxel in pre-treated metastatic breast cancer patients: a phase II study.

PURPOSE: This is a phase II study where a novel chemotherapy combination was tested in pre-treated breast cancer patients: docetaxel and irinotecan have already been established as agents for breast and colorectal cancer, respectively. METHODS: Forty-eight (median age 54 years, range 26-77 year) patients, all evaluable, were enrolled. All patients had been pre-treated with anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel and 2 with docetaxel. World Health Organization (WHO) performance status was 0-2. The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan infusion 200 mg/m(2) for 90 min and docetaxel infusion 80 mg/m(2) for 90 min, repeated once every 3 weeks. RESULTS: Twenty-five (52.08%, 95% confidence interval [CI] 37.95-66.21) patients showed responses: 3 complete (6.25%, 95% CI 0-13.05) and 22 (45.83%, 95% CI 31.74-59.92) partial; the most responsive metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia and fatigue were common; grade 3 diarrhea was observed in only one (2.08%) patient. CONCLUSION: The irinotecan-docetaxel combination produces quite a high response rate in pre-treated advanced breast cancer patients.

Paclitaxel combined with cis-platin as second-line treatment in patients with advanced non-small cell lung cancers refractory to cis-platin.

We combined paclitaxel with cis-platin as second-line treatment in patients with non-small cell lung cancer (NSCLC) who had previously undergone first-line therapy with cis-platin combined with cytotoxic drugs other than taxanes. The aim was to evaluate the effect of this cytotoxic combination in patients with refractory tumour to cis-platin. All 36 patients in the study population were evaluable for toxicity and 35 for response. Nine patients were stage IIIa, 15 IIIb and 12 IV. Prior treatment involved cis-platin plus vindesine and epirubicin or vinblastine and mitomycin-C; second-line treatment involved cis-platin (90 mg/m2) and paclitaxel (175 mg/m2), administered once every 3 weeks with 2-6 courses per patient. Partial response (40%) was obtained in 14 patients, 8 of whom had achieved minor response or stable disease after first-line treatment. Response duration was a minimum of 3 months. Toxicity was tolerable; only neurotoxicity was grade II in 16.7% of the patients. On the basis of our results, paclitaxel can be recommended as a very effective cytotoxic drug for NSCLC patients.

Inhibition of adriamycin cardiotoxicity by 5-fluorouracil: a potential free oxygen radical scavenger.

Adriamycin (ADR), a broad spectrum anticancer agent, has a limit to total dose used, due to cumulative cardiotoxicity. This side effect has been tested in the present study in combined administration with 5-fluorouracil a cytotoxic drug that often is applied together with ADR in cancer treatment. The study was performed on Wistar rats, and the experiment consisted of weekly administration for 12 weeks of adriamycin alone, of 5-fluorouracil alone, a combination of both, and a control group (normal saline) in separate groups comprising 42 animals each. The histology of the cardiac muscle, large vessels and liver, biochemistry of serum cholesterol, triglycerides and HDL-C and oxygen free radical production were examined. It was found that addition of 5-FU to the ADR administration reduced significantly the cardiac lesions, delayed and reduced the increase of serum lipids, produced by ADR alone and oxygen free radical production was also reduced, indicating that 5-fluorouracil is acting as a scavenger of free radicals.

Induction chemotherapy in non small cell lung cancer stage IIIa-b and IV and second-line treatment.

This study investigates the treatment management and survival of inoperable advanced non-small cell lung cancer (NSCLC) patients. The objective was to treat all patients with induction chemotherapy and then to stratify them for surgery, radiotherapy, second-line chemotherapy or supportive treatment. Of the 359 patients enrolled in the study, 336 fulfilled the study criteria and were classified as follows: 90 stage IIIa, 135 stage IIIb and 111 stage IV. Histological types included 131 squamous cell, 123 adenocarcinomas, 53 undifferentiated non-small, 15 large cell, 3 adenosquamous, 3 bronchoalveolar and 8 unclassified. For all patients induction therapy involved Cisplatin (CDDP) combined chemotherapy and 84% of the patients were also treated with Vindesine and Epirubicin. The mean number of courses was 4 (minimum 2, maximum 11). The result of induction therapy was 49% complete and partial for at least 8 weeks; with minor response included, the total response rate was 67.6%. Fourteen patients (4.16%) achieved analytically complete response, 151 (45%) partial response and 62 (18.5%) minor response. The second-line treatment implemented was as follows: surgical excision, 22 patients (Group A); radiotherapy, 106 patients (Group B); chemotherapy, 91 patients (Group C) and supportive treatment, 117 patients (Group D). Median survival in months was 72 (range 5-120+), 12 (range 2-118), 15 (range 3-48) and 7 (range 3-120) for Groups A-D respectively. There was a statistically significant difference in survival in Group A patients (p < 0.001) but no difference was observed between Groups B and C. Group D patients had significantly lower survival than the other three groups. In conclusion, induction chemotherapy renders a reasonably high response rate in operable NSCLC patients and second-line radiotherapy treatment is not superior to second-line chemotherapy.

Intramedullary spinal cord metastases in breast carcinoma: report of two cases and review of the literature.

Intramedullary spinal cord metastases (ISCM) are usually the result of rapidly progressing systemic malignancy. Breast cancer is one of the most common solid tumors with a high propensity of CNS dissemination. In the present report we describe two new cases with advanced breast cancer developing ISCM after a variable disease course. One of these patients had brain metastases at presentation, while at relapse developed leptomeningeal carcinomatosis which was treated successfully, but followed shortly, as a terminal event, by ISCM and parenchymal brain recurrence. The other patient was treated initially for locally advanced breast cancer and after multiple locoregional relapses, she developed liver metastases and subsequent ISCM and asymptomatic parenchymal brain deposits. Both patients experienced a rather rapidly evolving disease course leading to death 2 and 4 months, respectively, after widespread neuraxis dissemination of their cancer. Both these cases, added to the list of the anecdotally reported cases of ISCM after breast cancer, undermine the ominous prognosis and limited treatment options available for this disease manifestation, and an extensive literature review and discussion of similar cases is provided.

Chemotherapy-induced complete regression of choroidal metastases and subsequent isolated leptomeningeal carcinomatosis in advanced breast cancer: a case report and literature review.

Choroidal metastases from breast cancer represent an unusual metastatic presentation that has been traditionally treated with radiation therapy. Herein, we report a case of metastatic breast cancer presenting with pulmonary, cutaneous, lymph node and symptomatic choroidal metastases treated with systemic combination chemotherapy incorporating docetaxel and mitoxantrone without induction or consolidation radiation therapy to control visual symptoms from choroidal metastases. The patient experienced a durable complete remission in all metastatic sites that was maintained for 21 months since the initiation of chemotherapy, afterwhich she developed isolated leptomeningeal carcinomatosis managed successfully with intensive intrathecal methotrexate and whole brain irradiation leading to a new complete remission maintained until this report; 11 months after its presentation. This is the first case to our knowledge reporting complete regression of choroidal metastases with docetaxel-based chemotherapy as the only treatment modality and subsequent isolated leptomeningeal carcinomatosis recurrence.

Pregnancy and offspring after the appearance of breast cancer.

The objective of this study was to investigate the influence of pregnancy in breast cancer prognosis of women under the age of 35 years. Two hundred and forty-three women with breast cancer, from three oncology departments in Athens, were investigated. Twenty-one got pregnant (7.91%) 7-100 months after breast cancer diagnosis and in a median time period of 31 months. All women had mastectomy apart from 2 who had only lumpectomy as surgical procedure. Thirteen of 21 were treated with radiotherapy and 17 of 21 had also adjuvant chemotherapy mainly with CMF for 6 cycles. Sixteen children from 14 mothers were born and the rest of the patients underwent an abortion between the 2nd and 5th month of pregnancy. All children were healthy and grew up normally up to the age of 12-142 months (end of the study) and their median age of 51 months. Only 2 patients had stage III disease at diagnosis while the remaining 19 had stage I-IIb. Three cancer recurrences were observed (14.3%) after 7-84 months. One patient had a second primary-ovarian cancer 60 months after mastectomy. Recurrence rate and survival compared with those of nonpregnant women of the same age and the stages of disease were not different. To conclude: the present study indicates that healthy offsprings can be delivered from breast cancer patients, and pregnancy does not seem to play any role in tumor recurrence.

Phase I study of dose-escalated paclitaxel, ifosfamide, and cisplatin (PIC) combination chemotherapy in advanced solid tumours.

Based on the already known in vitro synergy between paclitaxel (taxol), cisplatin and oxazophosphorine cytostatics and the broad spectrum of activity of the above drugs we sought to evaluate the paclitaxel (taxol)-ifosfamide-cisplatin (PIC) combination in the outpatient setting in individuals with a variety of advanced solid tumours. Cohorts of patients were entered into six successive dose levels (DLs) with drug doses ranging as follows: paclitaxel 135-215 mg m(-2) day 1 - (1 h infusion), ifosfamide 4.5-6.0 g m(-2) (total dose) - divided over days 1 and 2, and cisplatin 80-100 mg m(-2) (total) - divided over days 1 and 2. Granulocyte colony-stimulating factor was given from day 5 to 14. Forty-two patients were entered. Eighteen patients had 2-8 cycles of prior chemotherapy with no taxanes or ifosfamide (cisplatin was allowed). The regimen was tolerated with outpatient administration in 36/42 patients. Toxicities included: grade 4 neutropenia for < or = 5 days in 27% of cycles; 5 episodes of febrile neutropenia in three patients at DL-III, -V and -VI. Grade 3/4 thrombocytopenia and cumulative grade 3 anaemia were seen in 7% and 13% of cycles respectively. Three cases of severe grade 3 neuromotor/sensory neuropathy were recorded at DL-II, -III, and -V, all after cycle 3. The maximum tolerated dose was not formally reached at DL-V, but because of progressive anaemia and asthenia/fatigue, it was decided to test a new DL-VI with doses of paclitaxel 200 mg m(-2), ifosfamide 5.0 g m(-2) and cisplatin 100 mg m(-2); this appeared to be tolerable and is recommended for further phase II testing. The response rate was 47.5% (complete response + partial response: 20/42). The PIC regimen appears to be feasible and safe in the outpatient setting. Care should be paid to neurotoxicity. Phase II studies are starting in non-small-cell lung cancer, ovarian cancer and head and neck cancer at DL-VI.

A phase II study of paclitaxel-ifosfamide-cisplatin combination in advanced nonsmall cell lung carcinoma.

BACKGROUND: The necessity to develop more effective chemotherapy regimens in advanced nonsmall cell lung carcinoma (NSCLC) prompted the authors to evaluate the paclitaxel-ifosfamide-cisplatin (PIC) combination, developed on the basis of high individual single-agent activity, in vitro synergism, and tolerance as determined in a previous Phase I study by the authors. PATIENTS: Eligibility criteria included advanced NSCLC (American Joint Committee on Cancer [AJCC]/International Union Against Cancer [UICC] Stage III/IV), Eastern Cooperative Oncology Group performance status (PS) /= 10,000/microL. RESULTS: Fifty patients were entered, and all were evaluable for response and toxicity: median age, 58 years (range, 40-72), PS, 1 (range, 0-2), Gender: 44 males and 6 females, Stages IIIA, 6 patients; IIIB, 17; IV, 27; histologies: adenocarcinoma, 27 patients; squamous, 17; large cells, 5; unspecified, 1. Metastatic sites at diagnosis included lymph nodes, 33 patients; bone, 6; liver, 5; brain, 10; lung nodules, 7; adrenals, 6; other, 2. Thirty-two of 50 (64%; confidence interval, 50.7-77.3%) evaluable patients responded: 4 complete remissions, 28 partial remissions, 13 stable disease, and 5 progressive disease. The quality-of-life score improved in 37 of 50 (74%) patients. The median response duration was 7 months (range 2-34+); median time-to-progression, 8 months (range, 1-36+), median overall survival, 12 months (range, 2-36+). One-year survival was 53%. Grade 3 and 4 toxicities included neutropenia 38 of 50 patients with 21 developing Grade 4 neutropenia (