Quality of life, Functional Assessment of Cancer Therapy-General.

Research on quality of life (QOL) in Thailand is still in its developing stages and requires cross-culturally valid QOL questionnaires to appropriately assess QOL as an endpoint in research and clinical trials. The English-language version of the FACT-G (Version 4) questionnaire was translated into Thai using an iterative forward-backward translation process. To determine if this instrument could cross a broad cultural divide and be used in Thailand, the reliability and validity of its Thai version was studied. The translated questionnaire was administered to 364 cancer patients. In evaluating its psychometric properties, internal consistency by Cronbach's alpha and test/retest reliability measured by Spearman rank-correlation coefficients were used. Cronbach's alpha coefficient ranged from 0.75 to 0.90. Spearman rank-correlation coefficient value for global QOL was 0.80. Validity was checked using two methods: factor analysis and known-groups comparison. Known-groups comparison analysis showed discrimination between subgroups of patients differing in clinical status as defined by disease stage (stage I/II vs stage III/IV, p < 0.001), treatment status (active treatment vs no treatment, p < 0.05), and financial burden (yes vs no, p < 0.001). In conclusion, the finding of this study indicate that the Thai version of the Functional Assessment of Cancer Therapy-General (FACT-G) is a reliable and valid measure of quality of life in cancer patients and can be used in clinical trials and studies of outcomes research in oncology.

High dose chemotherapy and peripheral blood stem cell transplantation for high risk primary breast cancer: a single center experience in Thailand.

Twenty patients with high risk primary breast cancer underwent a high dose chemotherapy program at Ramathibodi Hospital, Bangkok. Eligible patients included 21 women who had a histological diagnosis of breast cancer with more than 10 axillary lymph nodes involved. The patients first underwent modified radical mastectomy, followed by conventional doxorubicin containing adjuvant chemotherapy, before entering the treatment program. Peripheral blood stem cells were mobilized with cyclophosphamide and G-CSF and were harvested by leukapheresis. High dose chemotherapy consisted of cyclophosphamide 5,625 mg/m2, cisplatinum 165 mg/m2 and carmustine (BCNU) 600 mg/m2 were subsequently given, followed by infusion of the harvested peripheral blood stem cells. The median duration of cytopenia after transplantation was 8 days (range 7-12). The median expense for the transplantation, in addition to the cost of mastectomy and conventional chemotherapy, was 224,396 Baht (approximately US $5,350). Three out of the first four patients developed interstitial pneumonitis within three months after transplantation. There was one fatal case which was the only regimen related mortality. BCNU was then reduced to 450 mg/m2 and lung complications were markedly reduced afterwards. The median follow up time was 37 months with a median disease free survival of 38 months and overall survival of four years at 84%.

Clinical activity and benefit of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma pre-treated with fluorouracil-based chemotherapy.

The purpose of this prospective study was to assess the efficacy, clinical benefit and safety of irinotecan (CPT-11) in patients with 5-fluorouracil-resistant metastatic colorectal cancer (CRC). Sixteen patients with World Health Organization (WHO) performance status < or = 2 were treated with CPT-11 350 mg/m2 every 3 weeks. The observed partial response (PR) rate was 6.3 per cent with a high rate of stable disease (SD) (43.7%) which was of long duration (21.1 weeks for the best response; 1PR, 7SD). The median survival time for the 16 patients entered into this study was 69.6 weeks. There was no toxic death. The most frequent adverse events were neutropenia (31% grade 3/4) and delayed diarrhea (9.7%). CPT-11 has definite activity in the treatment of progressive metastatic CRC truly resistant to 5-FU which translated into clinical survival benefit. Median survival from first administration of CPT-11 was 78.6 weeks for patients with best response (PR + SD) compared with 28.1 weeks for patients with progressive disease (PD) (P = 0.01). With the appearance of new active drugs in this highly chemotherapy-resistant disease, the definition of response should be reassessed in CRC.

Effects of paclitaxel and carboplatin on quality of life and survival in patients with advanced non-small-cell lung cancer.

The purpose of this phase II study was to determine the effects of paclitaxel plus carboplatin administered by short duration on response rate, toxicity, and quality of life (QOL) in patients with non-small cell lung cancer (NSCLC). Twenty-seven patients were enrolled in this study. The objective response rate was 48.2 per cent, grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 22 per cent and 1.6 per cent, respectively. QOL was assessed in nineteen patients who completed six cycles of chemotherapy. Quality of Life Index (QLI) after six cycles of treatment showed no significant change from the baseline QOL. Compliance with the QOL protocol in this study diminished with the course of chemotherapy which is comparable to the literature figure. Thus, withholding current effective chemotherapy in patients with NSCLC with good performance status is no longer justified.

Phase II study of concurrent chemoradiotherapy for inoperable (bulky) stage III (A/B) non-small cell lung cancer (NSCLC): a preliminary report.

We designed a phase II study to determine the feasibility and toxicity of concomitant radiotherapy and Paclitaxel/Carboplatin followed by adjuvant chemotherapy of the same regimen in patients with newly diagnosed inoperable stage III A/B non-small cell lung cancer. Patients were irradiated with a total dose of 66 Gy. Weekly courses of Paclitaxel 45 mg/m2 and Carboplatin AUC 2 were administered intravenously during the irradiation period. After completion of concurrent chemoradiotherapy, adjuvant chemotherapy with Paclitaxel 175 mg/m2 and Carboplatin AUC 6 intravenously every 3 weeks for 4 cycles were given. Since March 1998, 15 patients have been enrolled. All patients were assessable for efficacy and toxicity after concurrent chemoradiotherapy. Eleven patients were assessable for efficacy and toxicity after adjuvant chemotherapy. After concomitant chemoradiotherapy, complete response (CR) was documented in 2 of 15 (13%). Partial response (PR) was documented in 9 of 15 (60%). After completion of adjuvant chemotherapy in 11 patients, the overall response rate was 91 per cent. (18% CR, 73% PR). There were 8 per cent gr. 3-4 neutropenia which occurred during adjuvant chemotherapy. Concomitant Paclitaxel/Carboplatin and radiotherapy are promising modalities in the treatment of inoperable stage III A/B non-small cell lung cancer.

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study.

This study was aimed to determine the activity and toxicity of combination paclitaxel and carboplatin in stage III B and IV NSCLC. Eligibililty required performance status. Paclitaxel was administered at a dose of 200 mg/m2, 3-hour infusion, followed by carboplatin at a tartgeted area under the concentration-time curve (AUC) of 6. Treatment was repeated at 3-week intervals for 6 courses. G-CSF 5 micrograms/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leukopenia or granulocytopenia in the previous course. From August 1996 through June 1997, 15 patients were enrolled. The median age was 47 years (range 20-68 years), 60 per cent were female. 73.3 per cent had adenocarcinoma, and 66.7 per cent had stage III B disease. Eighty three courses were administered; 13 patients (86.7%) completed all six cycles. The objective response rate was 53.3 per cent, with 1 (6.7%) complete response and 7 (46.7%) partial responses. Pleural effusion, lung lesion and lymph node were the three most common sites that responded to chemotherapy. The major toxicity was myelosuppression. Grade 3 or 4 granulocytopenia, anemia and thrombocytopenia were observed in 18 per cent, 7.2 per cent and 1.2 per cent, respectively, of 83 courses administered. Four episodes of febrile neutropenia (4.8%) occurred in 3 patients. There was one episode of anaphylaxis during Paclitaxel infusion. Other common toxicities were mild myalgia, paresthesias, alopecia and fatigue. Most of the toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.

Osteosarcoma: a study of 130 cases.

Multidisciplinary treatment of osteosarcoma in the Faculty of Medicine Ramathibodi Hospital, Mahidol University, using preoperative intraarterial and postoperative chemotherapy, with or without local irradiation, combined with surgery and prophylactic lung irradiation provided an excellent 5 years' survival of 55 per cent, the same rate as the 9 years' survival. The survival was stable after 4.4 years. The patients with local irradiation had more tumor destruction apparent on the surgical specimen. The administration of prophylactic whole lung irradiation provided an outcome without any undesirable complication. Sixteen per cent of the cases with PLI developed lung metastasis compared to 48 per cent without PLI. The most important prognostic factor was low level of serum lactic acid dehydrogenase. The unanswered question is what is the optimal treatment for osteosarcoma?

Ondansetron: prevention of nausea & vomiting in cisplatin based chemotherapy.

Ondansetron in the prophylaxis of Cisplatin-induced emesis and nausea. The 5-HT3 antagonist ondansetron clearly offers a new approach to the control of Cisplatin-induced emesis and has been evaluated in Thailand. To evaluate anti-emetic efficacy of ondansetron in the prevention of nausea and vomiting induced by Cisplatin containing cancer chemotherapy regimen, we carried out an open multicentre study from January 1991 to December 1992. In this study, patients receiving Cisplatin based chemotherapy received ondansetron 32 mg as a single intravenous dose over 15 minutes prior to the administration of Cisplatin. This was followed by oral ondansetron 8 mg three times a day, preferably one hour before each meal for 5 days. All patients were chemotherapy naive in-patients and were at least 18 years or older with Karnofsky performance status of at least 60 per cent. The number of emetic episodes, nausea and food intake were recorded during the 24 hours following Cisplatin administration. A total of 103 patients were recruited with 84 (81.6%) evaluable patients (48 men and 36 women) scheduled to receive cisplatin chemotherapy at dose 60 mg/m2 or more (60-100 mg/m2), either as single agent or combination therapy. Complete response (complete control of emesis) was achieved in 60 per cent; major response (1-2 emetic episodes) was 13 per cent; minor response (3-5 emetic episodes) was 13 per cent; and failure (5+ emetic episodes) was 10 per cent. Side effects were very mild and not significant. We conclude that ondansetron is efficacious in protecting patients from Cisplatin induced emesis and nausea.

Multidisciplinary "limb salvage" treatment of osteosarcoma.

Intraarterial plus systemic chemotherapy of cis-diamine dichloroplatinum-II and anthracycline together with preoperative radiation and "limb salvage" treatment have increased the chance of local control and facilitated the previous surgically nonresectable to be resectable. Among 30 cases of osteosarcoma from 1986-1989, aged 9-43 years old, 10 of the 17 cases (58.8%) are still alive with the mean disease free survival of 27.8 months. Late pulmonary metastases cause the need for future protocol for prophylactic lung therapy.

Nasopharyngeal carcinoma: results of treatment by radiotherapy vs chemotherapy plus radiotherapy.

To determine the efficacy of neoadjuvant chemotherapy over radiotherapy alone in locally advanced nasopharyngeal carcinoma, a prospective non-randomized study was performed from 1 January 1982 to 31 December 1985 at Ramathibodi Hospital, Thailand. There were 69 new cases who completed treatment and were followed up at least once. Thirty-three cases were treated by radical radiotherapy (RT) alone and 36 cases by chemotherapy (CT) + RT. CT were by the combination of cis-diamminedichloroplatinum II and 5 fluorouracil. Of 32 cases, 2 courses of CT were given before RT and 1 after. The other 4 received 3 courses prior to RT. For both groups, RT technique and dosage were similar. Follow-up time of both groups ranged from 6-104 months (mean 50.3, median 50) and 8-100 months (mean 52.2, median 54.5), and total failures were 18/33 and 13/36, respectively, with no statistical difference (p greater than 0.05). Estimated actual survival and disease free survival from Kaplan-Meier curves at 3 years were about 75 per cent vs 75 per cent and 65 per cent vs 65 per cent, respectively, with no statistical differences (Log-Rank test). Therefore, we concluded that induction chemotherapy had some benefit but no statistical significance over RT alone. However, the role of maintenance chemotherapy is now being studied.

Nasopharyngeal carcinoma: value of bone and liver scintigraphy in the pre-treatment and follow-up period.

Nasopharyngeal carcinoma (NPC) is a disease with a high potential of distant metastasis, especially to bone and liver. To evaluate the routine use of bone and liver scintigraphy in the evaluation of metastatic disease during the pre-treatment and follow-up period, 112 new cases of NPC were enrolled. The pre-treatment scintigraphs were performed at the time of staging evaluation, while the follow-up ones were performed once a year and whenever clinically indicated. At the pre-treatment period, 3/112 cases showed a true positive result, all at bony sites. At the 3 years follow-up, 10/83 and 8/83 cases respectively showed a true positive result in the bone and liver. All of the positive cases had definite symptoms and signs of metastases, which correlated well with the scintigraphic findings. All without clinical evidence showed a negative finding. Therefore, we conclude that, without clinical indication, routine bone and liver scintigraphy are of limited value.

Changes in T-staging of nasopharyngeal carcinoma by CT-scan.

To evaluate the value of computerized axial tomogram (CT-scan) of the nasopharynx in the management of patients with nasopharyngeal carcinoma (NPC), comparisons between clinical T-staging by means of indirect or direct nasopharyngeal examination, and CT-scan were performed in 101 cases. CT-scan has upstaged clinical T-staging in 83.9 per cent of Tx-T3 cases, or 80 per cent in Tx, 98 per cent in T1, 65.4 per cent in T2, and 50 per cent in T3 cases. CT-scan was also able to show the destruction of the base of the skull in 85.7 per cent of T4 cases. With regard to tumor extensions into the surrounding regions, the CT-scan proved to out-perform clinical T-staging by 82.2, 57.4, and 25.7 per cent respectively in superior, anterior, and lateral and inferior extensions. We, therefore, recommend that a CT-scan be done in every new case of NPC, because it provides more accurate T-staging, and more details of tumor extension, which is essential in the management of NPC, especially in the proper planning of radical radiotherapy.