Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma: a single institution experience from Thailand.

BACKGROUND: To report the results of combined chemoradiation (CCRT) with cisplatin versus carboplatin in locally advanced cervical carcinoma. METHODS: From 2009 to 2013, 255 patients with stage IIB-IVA cervical carcinoma, according to FIGO staging were prospectively assigned to be treated with pelvic radiotherapy followed by brachytherapy given concurrently with cisplatin or carboplatin in the treatment of locally advanced cervical cancer. Treatment outcomes and toxicitiy were evaluated. RESULTS: Two-hundred and thirteen patients could be evaluated. At a median follow-up time of 43 months (6-69 months), the 3-year local control, disease-free survival, metastasis-free survival and overall survival rates were 93, 80.8, 85.0 and 87.3 %, respectively. No statistical difference in terms of local control, disease-free survival, metastasis-free survival and overall survival rates between cisplatin and carboplatin treatments was observed in this study. Eighty-six percents of the patients in the carboplatin group could receive more than 4 cycles, while there were only 72 % in the cisplatin group who completed more than 4 cycles (p = 0. 02). In terms of acute toxicity, cisplatin caused significantly more anemia (p = 0.026), neutropenia (p = 0. 044) and nephrotoxicity (p = 0. 031) than carboplatin. No difference in late toxicity was observed in this study. CONCLUSION: Carboplatin yielded comparable results to cisplatin in concurrent chemo-radiation for locally advanced cervical cancer. In addition, carboplatin was associated with a better compliance rate and was associated with less of anemia, neutropenia and nephrotoxicity.

The effects of two HDR brachytherapy schedules in locally advanced cervical cancer treated with concurrent chemoradiation: a study from Chiang Mai, Thailand.

Efficacy of different schedules of HDR brachytherapy in concurrent chemoradiotherapy was evaluated. The study compared the effectiveness of the two HDR brachytherapy schedules which have the same Biological Effective Dose (BED) in locally advanced cervical carcinoma that was treated with concurrent chemoradiotherapy. Included in the study were 377 randomly selected patients with advanced carcinoma of the cervix uteri who were treated during the period 2004-2006. Patients were divided into Group I: 7.2 Gy × 3 fractions and Group II: 6 Gy × 4 fractions. With a median follow-up time of 35 months, local control, disease-free survival and overall survival rates were 80.8%, 63.4%, 98.8% in group I and 86.7%, 63.8%, 97.3% in group II, respectively. There was no statistical significance in terms of local control, disease-free survival, overall survival and complication rates between the two treatment schedules which could be observed. Seven patients in group I developed acute grade 2-4 GI toxicities and two patients in group II. In GU toxicities, there were three patients in group I and three patients in group II who developed grade 2-4 toxicities. In late toxicity, no patient developed grade 3-4 GU toxicities in group I while two patients developed grade 3-4 GU toxicities in group II. In GI toxicities, there were five and six patients in group I and group II, respectively, who developed grade 3-4 severity. Both HDR schedules seem to be safe and effective for the treatment of locally advanced cervical cancer.

Capecitabine and weekly paclitaxel as first-line therapy in Thai patients with metastatic breast cancer.

AIM: The combination of a taxane and capecitabine offers synergistic antitumor activity. This study aimed to determine the efficacy and tolerability of a paclitaxel and capecitabine combination in Thai patients with metastatic breast cancer (MBC) not previously treated for metastatic disease. METHODS: This open-label, single-center, non-comparative phase II study was conducted between December 2006 and March 2009. In all 40 MBC patients were treated with oral capecitabine 1000 mg/m(2) twice daily on days 1 to 14, and weekly paclitaxel 80 mg/m(2) in a 3-week cycle for a total of six cycles. RESULTS: After a median follow up of 13.4 months, an overall objective response rate of 80%, with a partial response of 74% and a complete response of 5% were achieved. While 8% of patients achieved stable disease, 13% had progressive disease. Median time to progress was 8 months and median overall survival was 24.4 months. One patient discontinued because of hypersensitivity to paclitaxel. There was no grade 4 toxicity. Skin and nail toxicity was found in 75% of patients (with 25% in grade 2 or 3), followed by neutropenia (45% in all with 15% in grades 2 or 3), neuropathy (25% in total with 5% in grade 2) and stomatitis and diarrhea (in both of which 5% experienced grade 1 severity). CONCLUSION: A first-line regimen of weekly paclitaxel plus capecitabine is effective and tolerable in Thai MBC patients.

Preliminary results of MRI-guided brachytherapy in cervical carcinoma: the Chiangmai University experience.

This study was performed to evaluate the feasibility of magnetic resonance imaging (MRI) in the treatment planning of image-guided brachytherapy for cervical carcinoma. Seventeen consecutive patients with locally advanced cervical cancer were enrolled in the study. Fifteen patients could be evaluated. When comparing the tumor at diagnosis (GTV-Dx) and the tumor at the first brachytherapy (GTV-BT), 11 of 15 patients showed a tumor regression of more than 80% while only four patients had less than 80% tumor regression. The mean D90 of HR-CTV and the calculated D2cc of the bladder, rectum, and sigmoid were 99.2 ± 11 Gy, 87.7 ± 5.7 Gy, 68.4 ± 5.4 Gy and 70.3 ± 6.8 Gy, respectively. No grade 3-4 acute toxicity was observed. The MRI can be a valuable tool for evaluating tumor response after external beam radiotherapy (EBRT) and is very helpful for prognosis prediction by residual GTV evaluation. Furthermore, MRI-guided brachytherapy allowed us to optimize the dose for both the target volumes and the OARs.

Preliminary results of conformal computed tomography (CT)-based intracavitary brachytherapy (ICBT) for locally advanced cervical cancer: a single institution's experience.

Intracavitary brachytherapy using tandem and ovoids is an important component of definitive treatment for cervical cancer. In the present study, we analyzed the dose-volume histograms (DVHs) of the tumor volume and organs at risk including the sigmoid colon by CT-based treatment planning for high dose rate (HDR) intracavitary brachytherapy (ICBT) in cervical cancer. Seventeen patients with carcinoma of the cervix uteri were treated with external beam radiotherapy plus concurrent chemotherapy. For brachytherapy, the planning procedure started by performing a conventional plan which prescribed a dose of 6.5-7 Gy per fraction to point A, then optimized the dose based on CT imaging. Volumes and DVHs were calculated for the HR-CTV, bladder, rectum and sigmoid colon. The mean BED(2Gy) total doses of post-optimized plans of HR-CTV, bladder, rectum and sigmoid colon were: 89.6, 94.1, 74.0 and 69.8 Gy, respectively. For conventional plans, the calculated mean BED(2Gy) total doses of HR-CTV, bladder, rectum and sigmoid colon were 92.2, 120.1, 75.7 and 78.3 Gy, respectively. This study showed statistical significant higher BED(2Gy) total doses for bladder and sigmoid colon (p < 0.001) using conventional plans versus post-optimized, CT-based plans, while no difference between HR-CTV and rectum BED(2Gy) total doses could be detected. After a median follow-up of nineteen months, all seventeen patients had a clinical complete response. Two patients developed distant metastasis. Compared with conventional treatment, CT based brachytherapy planning was very effective in reducing doses to OARs, especially bladder and sigmoid colon whilst maintaining a high therapeutic dose for tumor target volumes in the treatment of cervical carcinoma.

A retrospective study comparing hypofractionated radiotherapy and conventional radiotherapy in postmastectomy breast cancer.

BACKGROUND: The conventional radiotherapy (CRT) in postmastectomy breast cancer is 1.8-2.0 Gy daily for 25 fractions, while hypofractionated radiotherapy (HFRT) delivered dose in fewer fractions with larger radiation intensity. The present study compares the efficacy of HFRT and CRT. MATERIAL AND METHOD: From 2004 to 2006, 215 patients were retrospectively reviewed. Sixty seven patients received CRT and 148 patients received HFRT (2.65 Gy in 16-18 fractions). Five-year locoregional control (LRC), disease free survival (DFS), overall survival (OS) and toxicities were analyzed. RESULTS: Median follow-up was 39 months. Five-year LRC was 86.6% in CRT and 85.8% in HFRT (p = 0.852). Five-year DFS was 62.7% and 69.6% (p = 0.136) in CRTand HFRT respectively. Patients who received HFRT had significant increase in 5-year OS (62.7% and 73.0% (p = 0.048). No difference of toxicities including changes in chest wall appearance, skin fibrosis, brachial plexopathy, arm edema, pulmonary fibrosis, rib fractures and cardiovascular events was found between two groups. CONCLUSION: HFRT is as effective as CRT in postmastectomy breast cancer.

Impact of incomplete plan to treatment results of concurrent weekly cisplatin and radiotherapy in locally advanced cervical cancer.

To evaluate the efficacy of incomplete treatment protocols of cisplatin in concurrent chemoradiation for locally advanced cervical carcinoma. This retrospective study was performed in 165 consecutively treated patients with locally advanced cervical cancer who received a weekly cisplatin regimen. The number of weekly cisplatin cycles of each patient was recorded and used to discriminate between patients. Local control, disease free survival, distant metastasis-free survival, and toxicities were calculated using the software package SPSS version 15.0. Ninety-two patients (55%) completed the planned protocol of six cycles of weekly cisplatin. With the median follow-up time of 38.2 months, the 3-year local control rate differed significantly in the two patient groups (95.4% of 6 cycles versus 84.8% of < 6 cycles; p = 0.028). No statistical significance was observed for disease-free survival (74.6% versus 74.5%; p = 0.22) and distant metastasis-free survival (76.5% vs. 75.7%; p = 0.88). In conclusion, the plan completion of concurrent cisplatin with radiotherapy was responsible for better local control. However, differences in disease-free survival and distant metastasis-free survival were not statistical significant.

Phase II study of capecitabine (Ro 09-1978) in patients who have failed first line treatment for locally advanced and/or metastatic cervical cancer.

PURPOSE: The objective of this study is to evaluate the efficacy and safety of capecitabine in cervical cancer patients who have locoregional failure and/or distant metastasis and failed first line therapy. The efficacy of capecitabine is determined by the overall response rate (ORR) according to WHO criteria for response and the safety by adverse event (AE) and tolerability profiles according to NCI CTC version 2.0. PATIENTS AND METHODS: Patients with loco-regional failure and/or metastatic cervical cancer who have failed first line therapy were enrolled into the study. The patient received capecitabine 1, 250 mg/m2 twice daily for 14 consecutive days with 7 days rest (21-day cycle). The treatment was continued for up to six cycles. RESULTS: Forty-five patients previously treated by single or combination of surgery, or chemotherapy or radiotherapy were enrolled for study. Thirty-seven of 45 patients (82%) received at least 2 cycles of treatment and they were evaluated for response. The intention to treat analyses revealed 6/45(13%) ORR, 1/45 (2%) CR and 5/45 (11%) PR. Twenty-four patients (53%) had stable disease and 20% had progression of the disease. The median time to progression was 4. 1 months and the median overall survival was 9.3 months. CONCLUSION: Capecitabine as a monotherapy has a modest response in locoregional failure and/or metastatic cervical cancer who have failed first line therapy.

The study of cisplatin and vinorelbine in metastatic uterine cervical cancer.

OBJECTIVE: To determine the therapeutic efficacy of cisplatin in combination with vinorelbine in the treatment of patients with metastatic cervical cancer. MATERIAL AND METHOD: a total of 17 patients were enrolled in the present study. The median age was 46 years (38-65). There were 6 patients who were diagnosed as stage IVB cervical cancer without previous treatment. The patients were planned to receive cisplatin 80 mg/m2 on day 1 and vinorelbine at 30 mg/m2 on day 1 and 8 every 3 weeks. RESULTS: Fifteen patients were available for evaluation: 2 (13.3%) achieved a complete response, 8 (53.4%) partial responses, 3 (20%) stable diseases and 2 (13.3%) progression of the disease. Myelosuppression was the major toxicity Grade 3-4 toxicities include 66.7% hemoglobin and 26.7% neutropenia. No other significant side effects were found. CONCLUSION: Cisplatin-vinorelbine is an active and well-tolerated regimen in metastatic cervical carcinoma. These results require confirmation.

Taxotere, cisplatin, fluorouracil, and leucovorin (TPFL)as induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck.

UNLABELLED: This is a phase II clinical study conducted to evaluate the toxicity and efficacy of a 4-day regimen of docetaxel, cisplatin, fluorouracil, and leucovorin (TPFL) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Twenty-one previously untreated patients with stage III or IV SCCHN were treated with TPFL. Patients who received a complete response (CR) or partial response (PR) to three cycles of TPFL received definitive radiation therapy. The primary end points were toxicity and response to TPFL. RESULTS: Fifty cycles were administered to 21 patients. The major acute toxicities to TPFL were mucositis, fatigue, and anorexia. Additional major toxicities were neutropenia, anemia, and weight loss. The overall clinical response rate to TPFL was 47.6% , with 19% CRs and 28.6% PRs. In addition, the median time to progression and overall survival time were 49.2 months and 42.7 months, respectively. CONCLUSION: TPFL has an acceptable toxicity profile for patients with locally advanced squamous cell carcinoma of the head and neck and may hold curative potential for some patients with surgically unresectable or medical inoperable situations. OBJECTIVE: To evaluate the efficacy and safety to TPFL regimen for locally advanced squamous cell carcinoma of the head and neck.

Effect of oral pilocarpine on post-irradiation xerostomia in head and neck cancer patients: a single-center, single-blind clinical trial.

OBJECTIVE: The authors determined the efficacy and safety of oral pilocarpine tablet in symptomatic relief of post-radiation xerostomia in head and neck cancer patients. MATERIAL AND METHOD: Thirty-three radiation-induced xerostomia patients were enrolled in a single-blind method to receive placebo 1-tablet three times daily in the first month and then oral pilocarpine (5 mg) 1-tablet three times daily for the next three months. Patients were evaluated for subjective symptomatic relief of xerostomia using questionnaires. Objective findings of xerostomia were also evaluated at the same time by two radiation oncologists. RESULTS: All 33 patients had received radiotherapy doses at least 4000 cGy to the parotid glands. Improvement of xerostomia symptoms was observed, with a mean total subjective xerostomia score improvement at the first 4 weeks of oral pilocarpine treatment (p = 0.001), and later throughout the present study. Objective xerostomia score also showed statistically significant improvement at the same time point. Adverse effects of pilocarpine included sweating, nausea, palpitation, and tearing, with sweating as the most common side effect. Adverse effects of placebo included mild headache, nausea, and vomiting. CONCLUSION: Oral pilocarpine was effective and well tolerated in the treatment of radiation-induced xerostomia symptoms.

Preoperative irinotecan/5-FU/leucovorin plus concurrent radiotherapy in rectal cancer.

PURPOSE: To evaluate results of preoperative irinotecan/5-FU/leucovorin plus radiotherapy for locally-advanced rectal cancer. METHODS: Thirty-five patients with locally-advanced rectal cancer were treated with preoperative irradiation 46 Gy plus concurrent chemotherapy(irinotecan 10 mg/m(2)/d d1-d5, d22-d26, 5-FU 350 mg/m(2)/d d1-d5, d22-d26, and leucovorin 20 mg/m(2) d1-d5, d22-d26), followed by radical surgery. RESULTS: There were no treatment-related deaths. Acute toxicity was mainly in neutropenia and diarrhea, with both grade 4 neutropenia and grade 3 diarrhea observed in 4 patients(11%). Radical resectability was performed in 29 patients(83%)with sphincter preservation surgery in 7 patients. Six patients did not undergo the planned surgery due to patient refusal and disease progression. A complete pathological response was observed in 14%(4/29). Pathological T-downstaging was observed in 55%(16/29). CONCLUSIONS: These results suggest that preoperative radiochemotherapy with irinotecan/5-FU/leucovorin is safe and effective in tumor downstaging and allows sphincter-saving resection to be performed in locally-advanced rectal cancer.

FOLFIRI chemotherapy for metastatic colorectal cancer patients.

OBJECTIVES: 1) To confirm the efficacy of irinotecan plus folinic acid/continuous 5-fluorouracil as bimonthly FOLFIRI regimen in metastatic colorectal cancer patients. Efficacy evaluations will include response rate, duration of response, and survival. 2) To evaluate safety profiles on patients receiving this combination. MATERIAL AND METHOD: Nineteen patients with metastatic colorectal cancer received 180 mg/m2 intravenous (iv) day 1 of irinotecan, 200 mg/m2 iv of folinic acid, 400 mg/m2 iv bolus days 1 to 2, 5-fluorouracil (5-FU), and 600 mg/m2 iv 5-FU infusion over 22 hours, days 1 to 2. Treatment was repeated every two weeks and one cycle contained three fortnightly administrations. Sites of disease were liver in nine patients, lungs in three patients, bowels in four patients, lymph nodes in three patients, and peritoneum in two patients. Two patients had > 1 metastatic site. Previous treatments included adjuvant chemotherapy in seven cases and front-line chemotherapy for advanced disease in one case. RESULTS: A median of six treatment cycles was completed (range, 2-13 cycles). All patients were assessable for toxicity and 16 patients were evaluable for treatment response. The non-hematological toxicity was mild. Most had grade 1 or 2. Only one patient experienced grade 3 fatigue and anorexia, and discontinued chemotherapy after the second cycle. There were no cases with grade 4 toxicity. Fourteen patients had at least grade 2 alopecia. The most common hematological toxicity was neutropenia. Grade 3 and 4 neutropenia were observed in three and two patients, respectively. There was no case of febrile neutropenia. Based on intention to treat analysis, there were no complete responses (CR), five (26.3%) partial response (PR), and 11 (57.9%) stable disease. With the median follow-up of 6.6 months, the median time to disease progression was 4.7 months and the median survival time was 10.6 months. CONCLUSION: Bimonthly irinotecan in combination with folinic acid and 5-fluorouracil was active with acceptable toxicities and a prolonged survival time in pretreated colorectal cancer. Additional trials to define the optimal dose and schedule of treatment are justified.

Radiotherapy in Kimura's disease: a report of eight cases.

Kimura's disease is a rare condition of chronic inflammatory disorder affecting the skin and subcutaneous tissue. It is predominantly in the head and neck region. The lesion is benign but may be persistent/ recurrent and difficult to eradicate. Several forms of treatment have been used, including surgical excision, intralesional and oral corticosteroid, cryotherapy and radiotherapy. The authors report eight cases with histopathology consistent with Kimura s disease who received radiation therapy as a primary treatment or secondary treatment for recurrence after surgical excision in the Division of Therapeutic Radiology and Oncology, Chiang Mai University. The prescribed radiation doses varied from 30-40 Gy. With the mean follow-up time of 21 months, all eight patients were still free from disease at the time of analysis.

Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial.

PURPOSE: This single centre, open labelled, randomised non-inferiority trial compared concurrent chemoradiotherapy with carboplatin versus standard concurrent chemoradiotherapy with cisplatin in patients with locoregionally advanced nasopharyngeal cancer (NPC). PATIENTS AND METHODS: From August 1999 to December 2004, 206 patients with locally advanced NPC were randomised with 101 to cisplatin arm and 105 to carboplatin arm. Planned radiotherapy was the same in both groups. All the patients were evaluated for toxicity and survival according to the as-treated principle. RESULTS: With a median follow-up of 26.3 months (range 3-74.6 months), 59% of patients in the cisplatin arm completed the planned concurrent chemoradiation treatment, compared to 73% in the carboplatin arm. Forty-two percent of cisplatin patients completed the 3 cycles of adjuvant therapy compared to 70% in the carboplatin group. There were more renal toxicity, leucopenia, and anaemia in the cisplatin group, and more thrombocytopenia in the carboplatin arm. The 3 year disease free survival rates were 63.4% for the cisplatin group and 60.9% for the carboplatin group (p=0.9613) (HR 0.70, 95% confidence interval (CI): 0.50-0.98). The 3 year overall survival rates were 77.7% and 79.2% for cisplatin and carboplatin groups, respectively (p=0.9884) (HR 0.83, 95% CI: 0.63-1.010). CONCLUSION: We concluded that the tolerability of carboplatin based regimen is better than that of the cisplatin regimen. Moreover, the treatment efficacy of carboplatin arm is not different from the standard regimen in the treatment of locoregional advanced stage NPC.

Gemcitabine plus cisplatin (GC): a salvage regimen for advanced breast cancer patients who have failed anthracycline and/or taxane therapy.

BACKGROUND: In clinical studies of both heavily and minimally pretreated patients with advanced breast cancer, the combination of Gemcitabine plus cisplatin (GC), given in a variety of schedules and doses, has demonstrated moderate safety and efficacy in both heavily and minimally pretreated advanced breast cancer with response rate from 29-63% (median 46%). METHODS: We evaluated the activity and toxicity of another GC regimen (gemcitabine 1,000 mg/m(2) days 1, 8 plus cisplatin 75 mg/m(2) day 1 every 3 weeks) in 30 breast cancer patients who failed chemotherapy with anthracycline and/or taxanes as adjuvant or neoadjuvant, or primary therapy. RESULTS: We obtained overall response in 15 of 29 evaluable patients (52%), with responses occurring in all subgroups of disease (unresectable locally advanced, locoregional recurrence, and distant metastasis). Toxicity was primarily hematologic, with grade 3/4 neutropenia and thrombocytopenia in 37% and 17% of patients, respectively. The only grade 3/4 non-hematologic toxicity was grade 3 nausea/vomiting in 12% of patients. CONCLUSION: Our data suggest that gemcitabine plus cisplatin appears to be effective and has an acceptable toxicity profile in anthracycline and/or taxane pretreated patients with advanced breast cancer.

Oral cavity cancers at a young age: analysis of patient, tumor and treatment characteristics in Chiang Mai University Hospital.

Oral cavity cancer is predominantly a disease of middle-aged men who use tobacco and alcohol. Nearly 95% of carcinomas occur after the age of 45, with an average age of approximately 60 years. In recent years, oral cavity cancers have increased at a younger age, especially in females who never consumed alcohol or smoked. The purpose of this study is to provide the information of these cancers in young patients treated in our hospital during a 5-year period. As well as to describe the treatment modalities and their results. We reviewed the medical records of oral cavity cancer patients occurring before the age of 45 who were treated at Chiang Mai University Hospital from 1999 to 2003. All the demographic data, histopathology, treatment modalities and their results were recorded. Follow up range from 0.7 to 4.4 years (mean 2.6 year). A total of 20 patients were studied. There were 12 male (60%) and 8 female (40%). The mean age was 34.4 year (20-40 year). The most common site was oral tongue (15 patients, 75%). Fifty-five percent of patients were stage III and IV. Only 6 patients (30%) were treated by surgery alone, 8 patients (40%) were treated by surgery and post-operative radiotherapy, 4 patients (20%) were subjected to radiotherapy alone, and 2 patients (10%) were treated by radiochemotherapy. The results of primary treatment in all modalities were acceptable with 5 patients (25%) developing loco-regional recurrence of disease within 10.8 months (2-36). At the time of analysis, 13 patients (65%) had no evidence of disease. The demographic data of oral cavity in younger patients in our hospital were different from the elderly, with oral tongue commonly occurring. Most of the patients were locally advanced stage. The results of all treatment modalities provided fair loco-regional control suggested more aggressive treatment in this group of patients.

Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in head and neck cancer patients who had normal or mild impaired salivary gland function.

BACKGROUND: Amifostine has a potential role for salivary gland protection in head and neck cancer patients who had radiotherapy. MATERIAL AND METHOD: Sixty-seven head and neck cancer patients were randomized to receive radiotherapy or radiotherapy plus Amifostine. The efficacy of the treatment was determined by a questionnaire evaluating dryness of mouth and the oral comfort, the RTOG/EORTC acute/late radiation morbidity scoring criteria, collection of the whole saliva and the 99mTc-pertecnetate scintigraphy of the salivary glands. RESULTS: Amifostine significantly reduced the mean questionnaire scores from 6.49 to 3.73, the incidence of grade > or = 2 mucositis from 75% to 36% and acute xerostomia from 82% to 39%. The salivary gland function returned to normal at a rate of 36.3% in the Amifostine group versus 9.1% in the control group. CONCLUSION: Amifostine is effective in reducing the incidence and severity of acute mucositis, acute and late xerostomia in head and neck cancer patients.

Cisplatin and gemcitabine in patients with metastatic cervical cancer.

PURPOSE: To determine the therapeutic efficacy of cisplatin plus gemcitabine in the treatment of patients with metastatic cervical cancer. METHODS AND MATERIALS: A total of 51 patients were enrolled in this study. The median age was 46 years (34-67). Thirty-five patients were previously treated to the pelvis by radical radiotherapy, one patient was treated by surgery and one by surgery and postoperative radiotherapy. There were 14 patients with stage IVB cervical cancer who were previously untreated. The sites of metastases were 10 in the lungs, 5 in the supraclavicular nodes, 9 in the paraaortic nodes, 4 in the liver, 3 in the inguinal nodes, 5 in both supraclavicular nodes and lungs, 9 in both supraclavicular and paraaortic nodes, 1 in both supraclavicular and inguinal nodes, 1 in both lung and inguinal nodes, 2 in both lung and paraaortic nodes and 2 in both liver and lungs. Fine needle biopsies were done in all metastatic sites except for multiple lung and multiple liver metastases. Cisplatin was administered as an i.v. infusion on day 1 (70 mg/m2). Gemcitabine was administered as an i.v. infusion for over 30 minutes on day 1 and 8 (1,250 mg/m2) in a 21 day cycle. RESULTS: Forty patients were available for evaluation, with 3/40 (7.5%) achieving a complete response, 27/40 (67.5%) achieving a partial response (OR=30/40, 75%), 5/40 (12.5%) having a stable disease, and 5/40 (12.5%) a progressive one. Eleven patients were not assessable because of patient refusal for further treatment and loss of follow up. Myelosuppression was the major toxicity. Grade 3 or 4 anemia and granulocytopenia occurred at a frequency of 25.5% and 29.4%, respectively. Grade 3-4 thrombocytopenia was found in 3.8%. There were 3 (5.8%) patients who developed grade 4 neutropenia and fever. No other major side effects were found other than alopecia and usual gastrointestinal toxicities such as anorexia, nausea and vomiting. There were no treatment related deaths. The median time to progression was 8.3 months and the median survival was 9.6 months. With a median follow up of 7.7 months (range, 0.3 to 22.1), 30% of the patients were alive at 12 months. CONCLUSION: In this study of patients with metastatic cervical cancer, the combination of cisplatin and gemcitabine treatment induced a high response rate.

Combination of vinorelbine + doxorubicin in advanced breast cancer.

OBJECTIVE: To assess the efficacy of a vinorelbine + doxorubicin combination in terms of response rate and time to progression in patients with locally advanced or metastatic breast cancer. METHODS: Vinorelbine (25 mg/m2) and doxorubicin (25 mg/m2) were administered intravenously in a rapid injection on days 1 and 8 every 21 days. Initially, 3 courses of vinorelbine + doxorubicin were given. Patients with responding or stable disease received 6 more courses to a maximum of 9 courses. RESULT: Twenty-nine patients were entered into the study and 27 eligible patients were considered evaluable for response. Median age was 45 years (range 33 to 63). Overall response rate was 66.67% (18/27) (CR = 5, PR = 13). Median time to progression was 7.8 months (range 4 to 16) and the median survival time was 25.9 months. Median follow-up time was 8.5 months (range 1.5 to 25). Toxicity was generally moderate. Hematologic complication was the dose limiting toxicity. WHO grade III/IV neutropenia was observed in 18.5%/3.7% of patients. The major non-hematologic toxicities were nausea and phlebitis. Grade III nausea/vomiting was observed in 7.4% and grade III/IV phlebitis in 3.7%/3.7% of patients. No toxic deaths were observed. CONCLUSION: The present vinorelbine + doxorubicin combination was highly effective and generally well tolerated in cases of advanced breast cancer. Further studies are required.