14 THERAPY

News from the 34th Annual Meeting of the American Society of Oinical Oncology

LosAnge~ US; May 1998

Docetaxel combination as first-line therapy in ovarian cancer?

Paclitaxel in combination with a platinum agent is considered the standard first-line therapy for women with advanced ovarian cancer. Another first-line alternative may be on the way, according to results from a phase II clinical study of 111 women with previously untreated, advanced ovarian cancer.

In this study, conducted by Dr Paul Vasey and colleagues from the Beatson Medical Centre, Glasgow, Scotland, patients who had undergone cytoreductive surgery, received combination therapy with IV docetaxel 60-85 mg/m2 as a I-hour infusion plus carboplatin, both given once every 3 weeks for a total of 6 cycles.

An overall response rate of 67% was seen in 30 evaluable patients who had completed 6 cycles of therapy. Of these, complete and partial responses were seen in 40 and 27% of patients, respectively. 20% of patients had stable disease and 13% of patients had progressive disease.

Neutropenia, occurring in 86% of patients, was the most common adverse event; febrile neutropenia was noted in < 5% of patients. Importantly, the combination of docetaxel plus carboplatin was associated with a low incidence of neurotoxicity with 5% of patients experiencing neuropathy.

More studies needed Although these results are preliminary, they

strongly suggest that a paclitaxel plus carboplatin combination may be an effective first-line treatment option with a good tolerability profile for patients with advanced ovarian cancer, said Dr Vasey.

A prospective, randomised phase III trial comparing first-line therapy with either docetaxel plus carboplatin or paclitaxel plus carboplatin in women who have undergone surgery for advanced ovarian cancer is scheduled to start later this year. Beatson Medical Centre. Study dcmonstnlla TaxoII:re(R) /carbopla!in combination is active and safe as first·tiDe trealment for !ate.SIage ovarian

caDCer. Media Release: [2 pages], 19 May 1998 """'454

Docetaxel may increase survival in breast cancer

Single-agent therapy with docetaxel increased survival at 1 year by about 50% compared with vinblastine plus mitomycin combination therapy in women with breast cancer who participated in a multinational, phase III study.

The study involved 392 women with breast cancer whose disease had progressed during or after anthracycline therapy for advanced disease, or whose disease had relapsed ~ 1 year after receiving anthracycline-based chemotherapy.

The increase in overall survival in this study is 'impressive', according to the lead investigator

Inpharrna-30 --.y 1 .. No. 1138

Dr Jean-Marc Nabholtz from the Northern Alberta Breast Cancer Program, Edmonton, Canada [see table]. Docetaxel 'as a single agent. clearly demonstrated superiority to the combination therapy. This is very good news for patients with metastatic breast cancer whose cancer has progressed during or after anthracycline treatment' , he added.

Efficacy of docetaxel 'Os combination chemotherapy in women with metastatic breast cancer

Vlnblatlne plue Oocetaxal mltomyeln ~te

~n=l·i ~plente -.1n .. 203)

12·montt\ survival rate (percentage of pallents):

33 49

HI-month &UrvivaI rate (percentage 01 patients):

21 33

Overan f86POOse rate (percentage of patients):

12 30

TIme to cisease progression (weeks):

11 19

The tolerability profiles of both treatment options were predictable, said Dr Nabholtz. The most common adverse event was neutropenia. There was a higher incidence of thrombocytopenia, nausea, vomiting and constipation in recipients of the combination therapy. Docetaxel recipients had higher incidences of infections, stomatitis, diarrhoea, and fluid retention.

As the adverse event profiles were manageable for both treatments, then the risk:benefit ratio favours docetaxel monotherapy over combination therapy, said Dr Nabholtz. Cross Cancer lnstilUt.e. Alberta Cancer Board. Taxotere(R) inaeases breast cancer survival acc!rding 10 slUdy; ODe·year survival is 50 percent better !han cbemotbc:npy combination. Media Release: [2 pages I. 19 May 1998 ....,.,45'

Bica1utamide offers QOL benefits in prostate cancer

Monotherapy with bicalutamide 150mg once daily offers better quality of life (QOL) over castration in patients with advanced prostate cancer, according to the results of 2 studies presented at the meeting.

In the first study, subjective response data were obtained from 288 patients with symptomatic metastatic prostate cancer. Patient well-being was assessed using several scoring mechanisms including the level of cancer-related pain, cancer­related analgesic requirements and the ECOG performance status scale.

Favourable subjective responses were seen in 70% of bicalutamide recipients and 58% of patients who underwent castration (p = 0.046). This finding was statistically and clinically significant, according to the principal investigator Dr C Tyrell from Plymouth, England.

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THERAPY

In the second study. QOL was assessed using a 30-item questionnaire in patients receiving bicalutamide monotherapy or medical castration using combined androgen blockade (CAB) with go sere lin plus flutamide. Patients responded to questions including the effect of the disease (and subsequent treatment) on daily activities. fatigue. pain. sexual functioning. distress and social life. explained Professor Alessandra Rubagotti from the University and National Tumour Institute. Genoa. Italy.

Results from a preliminary evaluation of 18 preselected questions from 130 patients suggested improved QOL for bicalutamide recipients compared with CAB recipients at 3 and 6 months after treatment started. Assuming that a specific therapy is efficacious. other nonclinical factors such as convenience through once-daily administration, as well as reduced negative effects on QOL should also be considered. said Professor Rubagotti. ZcDCCa Pbarmaceuticals. New inyestigationalllUdies show lllOI1OIberapy wi1h Ca.sodex oilers quality-of-Iife beIldil over surgical castndioa in patients with

advanced prostale cancer. Media Release: [2 pages). 19 May 1998 --.-, ...

Photod~c therapy a shining light for NSCLC

Photodynamic therapy with porfimer sodium was approved by the US FDA in January 1998 for use in an additional indication. microinvasive endobronchial non-small-celliung cancer (NSCLC) in patients who are not candidates for surgery and radiotherapy. *

As a treatment for lung cancer. IV porfimer sodium selectively concentrates in tumour cells over a short period of time, while largely clearing from normal tissue after administration. Activation of the agent by non thermal laser light at the tumour site produces a toxic form of oxygen that destroys the cancer cells. The resulting necrotic tissue and exudate are subsequently removed 2 days later via a bronchoscope.

Oinical efficacy seen Clinical trial results from 102 patients with early­

stage lung cancer who received porfimer sodium photodynamic therapy were presented by Dr Stephen Lam from the British Columbia Cancer Agency in Vancouver. Canada. About 75% of porfimer sodium recipients had a biopsy-proven complete response to photodynamiC therapy, and about 50% of these maintained this positive response in long-term follow-up examinations. said Dr Lam. Most adverse events associated with the

procedure are of mild-to-moderate severity and are self-limiting; photosensitivity occurs in about 20% of patients, said Dr Lam. In addition. some patients experience inflammation at the treatment site which causes shortness of breath and coughing to varying degrees.

Phototherapy with porfimer sodium is 'an effective method for treating patients with early-stage lung cancer which minimises damage to surrounding normal tissue' , concluded Dr Lam.

• See /npharma 1122: 22. 3/ Jan 1998; lDJ631833

QLT Pbotothetapeutics Inc. QLT Phototherapeutics Inc. announces results

of Photofrin (R) lung cancer trials presented at ASCO Confc:rence in

Los Angeles. Media Release: [2 pages]. 20 May 1998 100677""

• Editorial comment: Poifimer sodium is already available in the US for use in the palliation of advanced oesophageal cancer.

Irinotecan: a new weapon against colon cancer

The only effective antineoplastic therapy for patients with colorectal cancer has been considered to be fluorouracil (5-FU). However, results from the first phase III study demonstrating that irinotecan monotherapy gives a better survival rate than 5-FU as second-line therapy in patients with advanced colorectal cancer were presented by Professor Eric Van Cutsem from the University Hospital Gasthuisberg. Leuven. Belgium.

In this multicentre study. 256 patients with advanced colorectal cancer, who had previously failed to respond to standard first-line therapy with 5-FU, were randomised to receive either IV irinotecan 350 mglm2/day every 2 weeks. or 1 of 3 regimens of IV 5-FU.

Survival improved at 1 year At I-year, the overall incidences of survival for

irinotecan and 5-FU recipients were 44.8 and 32.4%, respectively_ This translates to a 38% higher survival rate for irinotecan recipients. This demonstrates that irinotecan is the 'most active drug in advanced colorectal cancer as second-line treatment', said Dr Van Cutsem. These data show that irinotecan is 'a better therapeutic option than 5-FU for patients who receive second-line chemotherapy, and establishes a new reference for treatment' • he added. Interel Marien. New data demonstrates that CPT· II extends survival in people with advm::ed colon:cW caooer. Media Releue: [I pagel. 19 May 1998

Inphanna- 30 u.y 1188 No. 1138

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