Efficacy of pre-operative chemotherapy and sequential radiation therapy in irresectable rectal carcinoma

To evaluate the toxicity and relative response rates of addition of cisplatin to 5-fluorouracil and leucovorin preoperative induction chemotherapy followed by local radiotherapy in irresectable rectal cancer and their impact on radical resectability and sphincter preservation. Between January 2002 and April 2006, 29 patients with locally advanced unresectable rectal cancer received two cycles of 5-fluorouracil 600mg/m[2], I.V 6h infusion D[1]-D[5] and D[22]-D[26], Leucovorin 20mg/m[2], I.V 1h infusion D[1]-D[5] and D[22]-D[26] and cisplatin [CDDP] 60mg/m[2], I.V 6h infusion D[1] and D[22] after good hydration. Radiation treatment was administered after two weeks of the second cycle of chemotherapy. The dose was 45 Gray in 25 fractions over 5 weeks prescribed at isocenter of the plan to include the rectum and the draining lymph node chains. Tumor dimensions were assessed by CT scan before the start and 4 weeks after chemoradiotherapy. Tumor response classification was based on the standard World Health Organization criteria. Complete response [CR] is complete disappearance of the disease. Partial response [PR] is a decrease of 50% of the sum of the products of the greatest perpendicular diameters [SPD]. Progressive disease [PD] is appearance of a new lesion or an increase of 25% in SPD. Stable disease [SD] is no change in SPD or a change not reaching PR or PD. Overall response rate [ORR] is CR plus PR. Our regimen was well tolerated. The main toxicity to it was grade II hematological and grade II and III GIT toxicities in 31% and 65.5% respectively. PR occurred in 58.6% [17/29], SD in 20.7% [6/29] and PD in 20.7% [6/26]. Anterior resection of the rectum with total mesorectal excision and sphincter preservation was done in 37.9% [11/29], abdomino-perineal resection in 31.05% [9/29] and palliative colostomy in 31.05% [9/29]. Radical resectability was achieved in 62.1% [18/29] and cytoreductive surgery in 6.9% [2/29]. After 2 years follow up of resected cases, the 2 years disease free survival was 60% [12/20] with 25% [5/20] local recurrence rate and 15% [3/20] distant metastases to the liver. Our pre-operative combined modality therapy seems to have potential advantage in tumor response, local control and sphincter preservation with tolerable acute and chronic toxicity. Sequential use of chemo-radiotherapy needs more studies to estimate the maximum tolerable dose of chemotherapy and radiotherapy with least side effects

Concomitant boost radiation plus concurrent cisplatin for advanced head and neck carcinomas

This study was designed to assess the outcome of concurrent chemotherapy with a "concomitant boost" radiotherapy in the treatment of advanced unresectable head and neck cancer patients. Between January of 2001 and December of 2002, Thirty four patients who met the eligibility criteria were treated with combined chemoradiotherapy. Radiation consisted of 70 Gy in 40 fractions over a 6-week period [5 days / week for 4 weeks, then twice a day for 5 days for the last 2 weeks as a boost]. Concurrent chemotherapy was administered during weeks 1 and 5 of radiation therapy. Chemotherapy consisted of single agent cisplatinum. Cisplatinum was given as a daily bolus of 20 mg per square meter per day for 5 days for a total of 100 mg per square meter. Median follow-up was 22 months [6-48 months]. Complete response was recorded in 23 patients [68%] and 7 patients [21%] showed partial response. Median survival for the whole group was 30 months. The estimated 1 and 2 year rates of overall survival were 82.4% and 70.5% respectively. The median relapse free survival for complete responders was 28 months and the estimated 1 and 2 year rates of disease free survival were 80.4% and 58.4% respectively. Acute confluent mucositis [Radiation therapy Oncology Group [RTOG] grade 3] developed in 53% of patients. Long term toxicity is mainly based on xerostomia. Concurrent chemotherapy and concomitant boost radiotherapy approaches appear promising. The combination appears to be safe and effective in producing a good response, satisfactory local control and longer survival. Randomized trials comparing combined modality with the standard treatment are warranted to define the best treatment option in this group of patients with poor prognosis

comparative study of combination chemotherapy with docetaxel/cisplatin versus gemcitabine/cisplatin for locally advanced non-small cell lung cancer

Multiple concepts of combined modality therapy for locoregionally advanced inoperable non-small cell lung cancer [NSCLC] have been investigated. These include induction chemotherapy [CT], concomitant chemoradiotherapy [CRT], and intensified radiation therapy [RT] schedules. Concomitant chemoradiotherapy has led to promising results when combination chemotherapy regimens were used in the phase II setting. Induction chemotherapy followed by CRT has been proposed as one of the best treatment for locally advanced NSCLC, although both loco-regional and distant control of micrometastatic disease remains suboptimal. A comparative study was performed to investigate the efficacy of neoadjuvant combination chemotherapy using docetaxel [D] and cisplatin [C] versus gemcitabine [G] plus cisplatin [C] in patients with locally advanced NSCLC and the radiosensitization effects of both docetaxel and gemcitabine. From January 2003 to July 2004, 22 eligible patients were recruited, excluding those with malignant pleural effusion or vena cava syndrome and brain metastasis. Patients were treated as follows: A] Neoadjuvant chemotherapy: Chemotherapy-naive patients with stage III NSCLC were randomized to receive either D 90 mg/m[2] over one hour, followed by C 80 mg/m[2] on day 1 [Arm I] or G 1250 mg/m[2] on days land 8, C 80 mg/m[2] on day 1 [Arm II]. Treatment was repeated every three weeks for 3 cycles for both regimens. B] Concomitant chemoradiotherapy: Responsive and stable patients received CRT in the form of D 36 mg/m[2] over one hour, or G 300 mg/m[2] on days 1,8,22 and 29 of radiotherapy for both arms [at least 4 hours before RT] which was given in a total dose of 60 Gy/6 weeks, in daily fractions of 2 Gy for 5 days/week. The median age was 61 years [range 48-73], M/F = 18/4; ECOG PS 0-1, [7-15]; histology: Sq.C.C.=10, adenocarcinoma=5, large cell=4, undifferentiated=3; stage IIIAN2= 10[45.5%], IIIB=12[54.5%]. Myelosuppression was the predominant toxicity. WHO grade 3-4 anemia, granulocytopenia and thrombocytopenia were observed in 9.1%, 18.2%, 27.3% of patients in arm I and 9.1%, 18.1%, 45.5% in arm II respectively. Sensory neuropathy developed in 27.3% of arm I. After CT cycles the objective response rates [ORR] were 63.6% [2 CR and 5 PR] and 54.5% [one CR and 5 PR] in arms I and II respectively. After the addition of CRT, the ORRs were increased to 72.7% and 63.6% in both arms respectively. At a median follow-up of 12.4 months, the one-year survival was 75% and 65% in both arms. This study demonstrated that CT followed by CRT for responsive and stable patients was feasible and effective for both arms. Neither esophagitis nor pneumonitis was dose-limiting toxicities with these treatment regimens and no other dose-limiting toxicities were observed. Moreover, the good tolerability profile has clinical implications in terms of patient quality of life

5-FU and mitomycin-C in conjunction with radiotherapy in patients with locally advanced pancreatic carcinoma

To evaluate the outcome of concomitant radiocemotherapy [RCT] in terms of treatment response, tolerability, possibility of subsequent surgical resection and survival in locally advanced pancreatic carcinoma. Twenty patients with locally advanced pancreatic carcinoma had been included in a prospective study. Patients had attended to Kas El Aini Center of Clinical Oncology and to the Menoufiya University Hospital and Liver institute, between September 1998 and December 2000. All patients were treated by RCT compirising 5400 cGy daily fractions of180 cGy 5 days a week, 5-Floruracil [5-FU] : 600mg/m2 by continuous intravenous infusion day 1-day 5 and Mitomycin-C': 10mg/m[2], i.v.-bolus day 2. Chemotherapy was repeated on day 29. patients were re-evaluated for the treatment outcome and the possibility of surgical resection 4 weeks after RCT Treatment response, toxicity and overall survival were the study end point. Twelve patients [60%] had decreased primary tumor size. Five cases appeared potentially respectable by CT and exp1plorative laparotomies were done but only four could be respected. The median survival of the study group was 10 months [range 4-21]. Themedian survival of patients who had undergone surgery was 19 ms [1421] response but appeared irresistible by the CT scan. The mediam survival of patients with stationary or progressive tumors was 6.5 ms [4-10]. The treatment applied in the study is feasible and have o significant acute toxicity. The respectability was improved but with no improvement of survival. Additional neoadjuvanl chemotherapy trials with new regimens may support the potential benefits of this line of treatmen